DNA Mutations

Note some links on this page are affiliate links, by clicking and purchasing the item it gives me a bit of pocket change . This is how I can save up to afford further testing

In April 2019 I purchased DNA Test Kit tellmeGen to try to get further answers once it was complete I put the data in Promethase and this is the data it spit out that were red flags. 

Note I have only listed anything above 2 magnitude.


rs56144125(G;G)
CLN2 disease (predicted)

Bad Repute
8.8 Magnitude
2018-08-02 Geno Modified
Pathogenic ClinVar Significance
1 Publications
TPP1 Genes
11 Chromosome
6617154 Position
8.8 Max Magnitude
2018-08-02 Rs Modified
plus Stabilized
plus Orientation

rs56144125, also known as c.509-1G>C, is one of two recessively inherited mutations in the TPP1 (aka CLN2) gene, one of which is present in ~80% of patients with CLN2 disease ( neuronal ceroid lipofuscinosis). Caregivers and families with a suspected CLN2 mutation-based patient are encouraged to reach out to patient advocacy groups and related healthcare practitioners, for example the Batten disease community or the CLN2 Connection, since CLN2-­specific disease management strategies can greatly impact patient outcomes when implemented in a timely and appropriate manner.

rs121907980(C;C)
Tay-Sachs disease (predicted)

Bad Repute
8.8 Magnitude
2017-11-08 Geno Modified
Pathogenic ClinVar Significance
HEXA Genes
15 Chromosome
72350517 Position
8.8 Max Magnitude
2018-12-06 Rs Modified
minus Stabilized
minus Orientation

Brown-Vialetto-Van Laere syndrome type 1 mutation; riboflavin treatment recommended

Including recommendation for immediate riboflavin supplementation.

Bad Repute
8 Magnitude
2017-07-10 Geno Modified
Pathogenic ClinVar Significance
SLC52A3 Genes
20 Chromosome
761065 Position
8 Max Magnitude
2018-12-06 Rs Modified
plus Stabilized
plus Orientation

rs137852870(A;A)
Maple Syrup Urine Disease

Bad Repute
8 Magnitude
2 Count
2017-11-04 Geno Modified
Pathogenic ClinVar Significance
BCKDHA Genes
19 Chromosome
41424582 Position
8 Max Magnitude
2018-12-06 Rs Modified
plus Stabilized
plus Orientation

rs137852870, also known as c.1312T>A, p.Tyr438Asn and Y438N, represents a rare variant in the BCKDHA gene on chromosome 19. The rs137852870(A) variant, when inherited recessively, is considered pathogenic for Maple Syrup Urine Disease. This variant is considered a founder mutation among the Old Order Mennonites of southeastern Pennsylvania. 23andMe name: i5004463

rs137853022(C;C)
Familial dysautonomia

Bad Repute
7.7 Magnitude
2017-12-15 Geno Modified
Other ClinVar Significance
IKBKAP Genes
9 Chromosome
108900303 Position
7.7 Max Magnitude
2017-07-17 Rs Modified
minus Stabilized
minus Orientation

rs137853022, also known as R696P or Arg696Pro, is a SNP in the inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase complex-associated protein IKBKAP gene. This is reported as one of two mutations accounting for 99% of the cases of familial dysautonomia in Ashkenazi Jews; in 2

rs137853097(T;T)
DBP deficiency (predicted)

Bad Repute
7 Magnitude
2 Count
2019-01-05 Geno Modified
Other ClinVar Significance
HSD17B4 Genes
5 Chromosome
119509176 Position
7 Max Magnitude
2019-01-05 Rs Modified
plus Stabilized
plus Orientation

aka c.1369A>T (p.Asn457Tyr or N457Y), and also c.1369A>G (p.Asn457Asp or N457D); the former is considered in ClinVar to be pathogenic, the latter likely to be pathogenic 23andMe name for c.1369A>T: i5007146

rs148591292(C;C)
Rhizomelic chondrodysplasia punctata type 1

Bad Repute
7 Magnitude
2 Count
2015-07-07 Geno Modified
Pathogenic ClinVar Significance
PEX7 Genes
6 Chromosome
136898242 Position
7 Max Magnitude
2018-12-06 Rs Modified
plus Stabilized
plus Orientation

PEX7 IVS9, G-C, +1 Rhizomelic chondrodysplasia punctata type 1 This SNP is called i5006214 and i6055954 by 23andMe.

 

rs113994097(C;C)
Ataxias, including spinocerebellar ataxia

Bad Repute
7 Magnitude
2 Count
2016-06-14 Geno Modified
Pathogenic ClinVar Significance
1 Publications
POLG Genes
15 Chromosome
89323426 Position
7 Max Magnitude
2018-12-06 Rs Modified
minus Stabilized
minus Orientation

rs113994097, also known as c.2243G>C, p.Trp748Ser and W748S, represents a mutation in the POLG gene on chromosome 15. Inherited in a recessive manner, the uncommon rs113994097(C) allele is associated with a variety of syndromes involving ataxias, including mitochondrial DNA depletion syndrome type 4A (Alpers syndrome) and sensory ataxic neuropathy, dysarthria, and ophthalmoparesis (SANDO). Haplotype analysis has demonstrated that the rs113994097(C) in patients from Finland, Norway, the United Kingdom, and Belgium appears to originate from a common ancient founder. 23andMe name: i5006731

rs34536443(C;C)
Much higher (90 fold) risk of developing tuberculosis if exposed to TB bacterium

Bad Repute
6.3 Magnitude
2019-01-04 Geno Modified
0.01423 GMAF
Probable non-pathogenic ClinVar Significance
11 Publications
TYK2 Genes
19 Chromosome
10352442 Position
6.3 Max Magnitude
2019-07-03 Rs Modified
plus Stabilized
plus Orientation

aka c.3310C>G (p.Pro1104Ala or P1104A) Inherited recessively, this variant appears to greatly increase (OR 89.3, CI: 14.7 – 1725, p=8.3x10e-8) the risk of developing tuberculosis according to a 2018 study, if the carrier of the minor homozygote genotype is exposed to the tuberculosis mycobacterium. The mechanism by which this occurs led to the suggestion that at-risk individuals could potentially prevent or treat the disease with gamma-interferon. In Europeans, one in 600 people have two copies of the rs10352442(G) variant, and in the rest of the world, the rate is estimated to be between one in 1,000 to one in 10,000. https://www.futurity.org/tuberculosis-genetic-mutation-1948622/

rs1801155(A;A)
Risk of colon cancer and familial adenomatous polyposis (FAP) which usually progresses to malignancy

Bad Repute
6 Magnitude
2017-06-24 Geno Modified
0.00108 GMAF
Other ClinVar Significance
10 Publications
APC Genes
5 Chromosome
112839514 Position
6 Max Magnitude
2018-12-06 Rs Modified
plus Stabilized
plus Orientation

also known as rs28933380; related to colorectal cancer. The APC I1307K mutation is primarily found in people of Ashkenazi Jewish heritage (Jews of Eastern European or Russian ancestry). Researchers believe that 6% of Ashkenazi Jews carry this gene mutation, making them at a significantly higher risk for developing colorectal cancer. It is also found among Sephardi and Mizrahi Jews and Muslim and Christian Palestinian Arabs, as well as Negev Bedouin. Many patients with colorectal cancer experience no symptoms in the early stages. In fact, symptoms may not appear until the disease is in advanced stage. Routine colorectal screening is very important. Even children from 11 years of age should be screened if there is a family history of colorectal cancer.
• APC I1307K and Colorectal Cancer – Johns Hopkins Hereditary Colorectal Cancer Website

Also known as rs28933380, related to colorectal cancer, FAMILIAL, Ashkenazi The APC I1307K mutation is primarily found in people of Ashkenazi Jewish heritage (Jews of Eastern European or Russian ancestry). Researchers believe that 6% of Ashkenazi Jews carry this gene mutation, making them at a significantly higher risk for developing colorectal cancer. It is also found among Sephardi and Mizrahi Jews and Muslim and Christian Palestinian Arabs, as well as Negev Bedouin. Many patients with colorectal cancer experience no symptoms in the early stages. In fact, symptoms may not appear until the disease is in advanced stage. Routine colorectal screening is very important. Even children from 11 years of age should be screened if there is a family history of colorectal cancer.
• APC I1307K and Colorectal Cancer – Johns Hopkins Hereditary Colorectal Cancer Website…

rs138249161(A;A)
Hypomyelinating leukodystrophy, type 8

Bad Repute
6 Magnitude
2015-09-19 Geno Modified
Pathogenic ClinVar Significance
POLR3B Genes
12 Chromosome
106432421 Position
6 Max Magnitude
2018-12-06 Rs Modified
plus Stabilized
plus Orientation

rs138249161, also known as c.1568T>A, p.Val523Glu and V523E, is a mutation in the POLR3B gene on chromosome 12. The minor (A) allele is a very rare variant, seen only 34 times out of 121358 alleles in ExAC, with 0 homozyotes observed and a MAF of 0.00028. When inherited recessively or as a compound heterozygote, the rs138249161(A) allele is considered a causative mutation leading to hypomyelinating leukodystrophy, type 8. See information at OMIM 614366.0005.

 

rs421016(G;G)
Gaucher disease; at least 5x higher risk of Parkinson’s

Bad Repute
6 Magnitude
2015-04-14 Geno Modified
Other ClinVar Significance
7 Publications
GBA Genes
1 Chromosome
155235252 Position
6 Max Magnitude
2018-12-05 Rs Modified
plus Stabilized
plus Orientation

rs421016, also known as L444P or Leu444Pro, is a SNP causing an amino acid change in the GBA gene; it is among the most common mutations associated with Gaucher disease of any type. Amino acid predictions from genome sequence may predict this as L483P or Leu483Pro; this disparity in position calling may be due to a 39 peptide signal sequence. Polyphen 2 predicts P04062 L483P to be “possibly damaging” with a score of 0.857 (sensitivity: 0.83; specificity: 0.93). ( P04062 is the uniprot ID for GBA.) The risk allele (in current dbSNP orientation) is (G), and as the inheritance is autosomal recessive, individuals must either be compound heterozygotes (for two different GBA mutations) or rs421016(G;G) homozygotes to develop Gaucher disease. There are over 300 mutations now known to occur in the…

rs104893931(T;T)

Bad Repute
6 Magnitude
2 Count
2015-08-01 Geno Modified
Pathogenic ClinVar Significance
SMN1 Genes
5 Chromosome
70938888 Position
6 Max Magnitude
2018-12-06 Rs Modified
plus Stabilized
plus Orientation

rs104893931, also known as c.131A>T, p.Asp44Val and D44V, is a mutation in the SMN1 gene on chromosome 5. The rare rs104893931(T) allele is a mutation associated with the recessively inherited type 3 spinal muscular atrophy. This SNP is referred to as i5005735 by 23andMe.

rs137852591(G;G)
Androgen insensitivity (possibly partial)

Bad Repute
6 Magnitude
2017-02-03 Geno Modified
Pathogenic ClinVar Significance
1 Publications
AR Genes
X Chromosome
67721909 Position
6 Max Magnitude
2017-08-07 Rs Modified
plus Stabilized
plus Orientation

Height related SNP; carriers of the (rare) minor allele for this SNP are approximately 2 cm shorter than non-carriers.

 

rs200179145(T;T)
Polycystic kidney disease

Bad Repute
6 Magnitude
2015-07-31 Geno Modified
Other ClinVar Significance
PKHD1 Genes
6 Chromosome
51903601 Position
6 Max Magnitude
2018-12-06 Rs Modified
plus Stabilized
plus Orientation

rs200179145, also known as c.6992T>A, p.Ile2331Lys or I2331K, is a SNP in the PKHD1 gene on chromosome 6. The risk allele, rs200179145(A), is considered causative for autosomal recessive Polycystic kidney disease. This SNP is referred to as i6016629 by 23andMe.

rs104893935(G;G)
Spinal muscular atrophy, type 1 or 2

Bad Repute
6 Magnitude
2 Count
2015-08-01 Geno Modified
Pathogenic ClinVar Significance
SMN1 Genes
5 Chromosome
70942416 Position
6 Max Magnitude
2018-12-06 Rs Modified
plus Stabilized
plus Orientation

rs104893935, also known as c.332C>G, p.Ala111Gly and A111G, is a mutation in the SMN1 gene on chromosome 5. The rare rs104893935(G) allele is a mutation associated with the recessively inherited type 1 or 2 spinal muscular atrophy. This SNP is referred to as i5005737 by 23andMe.

rs62642926(G;G)
Phenylketonuria

Bad Repute
6 Magnitude
3 Count
2015-04-13 Geno Modified
Pathogenic ClinVar Significance
PAH Genes
12 Chromosome
102912842 Position
6 Max Magnitude
2018-12-06 Rs Modified
minus Stabilized
minus Orientation

rs62642926, also known as c.117C>G, p.Phe39Leu and F39L, represents a mutation in the PAH gene on chromosome 12. The quite rare rs62642926(G) allele (as represented on the minus strand in GRCh37 and GRCh38) leads to phenylketonuria when inherited in two copies or as a compound heterozygote. See also OMIM 612349.0031 This SNP is renamed as i4000470 by 23andMe. FTDNA & MyHeritage name: VG12S8223

gs266

5 Magnitude
2017-08-12 Geno modified

Data Quality Warning Some of your data claims that you have 2 Y chromosomes. In particular it is claiming heterozygosity for a Y chromosomal SNP. While it is true that https://en.wikipedia.org/wiki/XYY_syndrome exists, the microarrays used by 23andMe, Ancestry.com and their analysis methods and others are prone to misinterpreting the sex chromosomes. As a result Promethease sometimes sees this in their raw data. At various times, Ancestry.com has previously addressed this at
• https://archive.is/eRE26#selection-935.6-939.41
• http://ancestryforums.custhelp.com/posts/b7de792b84?commentId=30021 (dead link) With a similar answer from 23andMe at https://www.23andme.com/you/community/thread/40845/ Even in those rare cases where you actually are XYY, it’s likely that microarray testing would fail to detect it. This is because our understanding is that the two Y chromosomes in an XYY individual should be duplicates of each other, since they come about from a nondisjunction event in meiosis (II). As duplicates, they shouldn’t show heterozygosity. In other words, even in an XYY individual, the Y chromosome SNPs should not show heterozygosity, which is why this genoset is a warning for poor data quality.

rs140291094(G;G)
Predicted to have Native American myopathy

Bad Repute
5 Magnitude
2014-11-14 Geno Modified
Pathogenic ClinVar Significance
1 Publications
STAC3 Genes
12 Chromosome
57244322 Position
5 Max Magnitude
2018-12-06 Rs Modified
plus Stabilized
plus Orientation

rs140291094, also known as Trp284 Ser or W284S, is a SNP in the SH3 and cysteine rich domain 3 STAC3 gene on chromosome 12. In 2013, rs140291094 was identified as a cause of Native American myopathy, a recessive condition. The common allele is rs140291094(C); the rare mutant is rs140291094(G).

 

rs121908936(A;A)
Congenital lactase deficiency This genotype is reported to lead to congenital lactase deficiency.

Bad Repute
5 Magnitude
2015-05-16 Geno Modified
Pathogenic ClinVar Significance
LCT Genes
2 Chromosome
135807131 Position
5 Max Magnitude
2018-12-05 Rs Modified
minus Stabilized
minus Orientation

rs137852695(T;T)
Neuronal Ceroid Lipofuscinosis

Bad Repute
5 Magnitude
3 Count
2015-01-07 Geno Modified
0.001377 GMAF
Pathogenic ClinVar Significance
PPT1 Genes
1 Chromosome
40091398 Position
5 Max Magnitude
2018-12-05 Rs Modified
minus Stabilized
minus Orientation

Neuronal ceroid lipofuscinosis (PPT1-related)

rs79761867(C;C)
Maple Syrup Urine disease

Bad Repute
5 Magnitude
3 Count
2014-12-25 Geno Modified
Other ClinVar Significance
1 Publications
BCKDHB Genes
6 Chromosome
80168945 Position
5 Max Magnitude
2018-12-06 Rs Modified
plus Stabilized
plus Orientation

rs79761867, formerly known as rs28934895 and more commonly known as R183P, is a mutation (rare SNP) in the branched chain keto acid dehydrogenase E1, beta polypeptide BCKDHB gene. The common allele is rs28934895(G), encoding arginine (R) at amino acid position 183. With a frequency of about 1 in 100 among Jews of European descent, the much rarer rs28934895(C) allele encodes a proline (P), and it is the most frequent mutation leading to Maple Syrup Urine Disease, accounting for perhaps 90% of the mutations in this population group. However, by itself the mutation does not predict the severity of the disease; note also that only homozygotes ( rs28934895(C;C)) are at risk for the disease. This SNP is often included in screening panels for carriers of deleterious mutations among Ashkenazi Jews…

rs33913413(G;G)
Beta Thalassemia intermedia likely; Hemoglobin beta-plus; variable clinical symptoms see HBB

Bad Repute
4.5 Magnitude
2017-05-17 Geno Modified
Pathogenic ClinVar Significance
7 Publications
HBB Genes
11 Chromosome
5225729 Position
4.5 Max Magnitude
2016-12-16 Rs Modified
minus Stabilized
minus Orientation

rs113993958(C;C)
Cystic Fibrosis (D110H); milder form

Bad Repute
4 Magnitude
2015-01-05 Geno Modified
Pathogenic ClinVar Significance
CFTR Genes
7 Chromosome
117530953 Position
4 Max Magnitude
2017-07-17 Rs Modified
plus Stabilized
plus Orientation

rs113993958, also known as c.328G>C, is a SNP in the CFTR gene potentially leading to a mild form of cystic fibrosis known as Asp110His or D110H ( OMIM 602041.0004). The common form is rs113993958(G), whereas the form leading (when present in two copies) to cystic fibrosis is rs113993958(C). named i5006048 by 23andMe, although their SNPs i5010823, i5010825 and i5010826 are also at the same nucleotide position

rs61749738(G;G)
possible: Rett syndrome

Bad Repute
4 Magnitude
2015-10-06 Geno Modified
Non-pathogenic ClinVar Significance
1 Publications
MECP2 Genes
X Chromosome
154031145 Position
4 Max Magnitude
2017-07-18 Rs Modified
minus Stabilized
minus Orientation

rs61749738, also known as c.719C>G, p.Thr240Ser and T240S, as well as c.683C>G, p.Thr228Ser and T228S, represents a rare mutation in the MECP2 gene, located on the X chromosome. Different sources differ on whether the rare rs61749738(G) allele leads to Rett syndrome, one of the most common forms of mental retardation in females. Some sources report that this allele is benign; others conclude it is pathogenic, including the authors of.

rs200604349(G;G)
recessive neurodevelopmental disorder

Bad Repute
4 Magnitude
2016-03-09 Geno Modified
SAMM50 Genes
22 Chromosome
43989164 Position
4 Max Magnitude
2016-03-09 Rs Modified
plus Stabilized
plus Orientation

rs2066845(C;C)
~35x higher risk for Crohn’s disease

Bad Repute
4 Magnitude
2014-01-02 Geno Modified
0.007805 GMAF
Other ClinVar Significance
41 Publications
NOD2 Genes
16 Chromosome
50722629 Position
4 Max Magnitude
2019-09-08 Rs Modified
plus Stabilized
plus Orientation

rs2066845 is a SNP in the NOD2 gene; this SNP is also known as c.2722G>C, G908R or Gly908Arg, with the (G) allele encoding the Gly (G) and the (C) allele encoding the Arg (R). The two initial reports linking the minor(C) allele as strongly associated with Crohn’s disease are and. rs2066845 has also been reported, with an odds ratio of 3.5 (CI 1.51–7.01), to be associated with psoriatic arthritis. In a 2018 publication, rs2066845 was reported to be associated with sarcoidoisis, possibly in conjunction with other variants in the IL17RA, KALRN and EPHA2 genes. No association was found for NOD2/CARD15 SNPs (R702W, G908R) in Chinese patients with inflammatory bowel disease.

rs144475004(C;C)
Significant (6x) increase in risk for psoriasis, at least in Asians

Bad Repute
3.5 Magnitude
2016-04-25 Geno Modified
1 Publications
CARD14 Genes
17 Chromosome
80184089 Position
3.5 Max Magnitude
2017-09-03 Rs Modified
plus Stabilized
plus Orientation

rs144475004, also known as c.526G>C, p.Asp176His and D176H, represents a variant in the CARD14 gene on chromosome 17. In 416 psoriasis patients, the rs144475004(C) allele was associated in Asian individuals with generalized pustular psoriasis (odds ratio 6.4, p=8.4×10e-5), but no CARD14 mutations were found to be associated with other forms of psoriasis vulgaris (PV) or with pityriasis rubra pilaris (PRP).

rs150414818(G;G)
increased risk of gout

Bad Repute
3.5 Magnitude
2011-10-12 Geno Modified
ALDH16A1 Genes
19 Chromosome
49465749 Position
3.5 Max Magnitude
2015-01-02 Rs Modified
plus Stabilized
plus Orientation

a low-frequency missense variant rs150414818 (c.1580C>G) in ALDH16A1 associated with gout (OR = 3.12, P = 1.5× 10?16, at-risk allele frequency = 0.019) and serum uric acid levels (effect = 0.36 s.d., P = 4.5× 10?21) nature genetics

rs12735723(G;G)
Variegate porphyria

Bad Repute
3.5 Magnitude
0% Frequency

2011-11-15 Geno Modified
0.004132 GMAF
Pathogenic ClinVar Significance
PPOX Genes
1 Chromosome
161169143 Position
3.5 Max Magnitude
2018-12-05 Rs Modified
plus Stabilized
plus Orientation

rs142129409(A;A)
Uncombable hair syndrome see uncombable hair syndrome

Bad Repute
3.3 Magnitude
2016-11-19 Geno Modified
Pathogenic ClinVar Significance
PADI3 Genes
1 Chromosome
17262194 Position
3.3 Max Magnitude
2018-12-05 Rs Modified
plus Stabilized
plus Orientation

Uncombable hair syndrome variant in PADI3 gene, c.335T>A or p.Leu112His

gs122

Bad Repute
3.1 Magnitude
2017-12-24 Geno modified

7x risk of male baldness 7x risk of baldness among men, according to. Baldness (“androgenic alopecia”) was defined as Hamilton grade V-VII alopecia seen in men between the ages of 35 and 65. The ability of this genoset to rule out going bald is reportedly high (in other words, if you are not positive for gs122, odds are good you will not go bald), but it is lacking in specificity (negative predictive value = 96.5%, positive predictive value = 12.2%, sensitivity = 98.2%, specificity = 6.6%).

rs1801166(C;C)
increased colon cancer risk? significance is unclear observed in an 18th century hungarian mummy

Bad Repute
3 Magnitude
2016-12-10 Geno Modified
0.003673 GMAF
Other ClinVar Significance
5 Publications
APC Genes
5 Chromosome
112839543 Position
3 Max Magnitude
2018-01-06 Rs Modified
plus Stabilized
plus Orientation

rs1801166, also known as c.3949G>C, p.Glu1317Gln and E1317Q, represents a rare variant in the APC gene on chromosome 5. There are conflicting views on whether the minor rs1801166(C) allele increases risk for familial adenomatous polyposis (FAP), a disorder often leading to colorectal cancer. One publication states the presence of this minor allele raises the risk of colon cancer 11 fold; other publications find no increase in risk. Note that normally, APC gene mutations associated with FAP are dominant (and highly penetrant). Given that, the most conservative conclusion would be to say that if it’s pathogenic at all, the E1317Q mutation is likely to lead to significantly increased risk primarily in rs1801166(C;C) homozygotes, but it might also be worth suggesting increased screening for heterozygotes anyway, and most especially for any E1317Q carriers with a family history of colon cancer. 23andMe name:…

rs113994096(C;T)
Carrier of a possible mutation for a mitochondrial syndrome, but significance unclear

Bad Repute
3 Magnitude
2017-01-05 Geno Modified
0.0009183 GMAF
Other ClinVar Significance
POLG Genes
15 Chromosome
89325639 Position
3 Max Magnitude
2018-12-06 Rs Modified
minus Stabilized
minus Orientation

Pathogenicity of the minor allele is in question; and, as a recessively inherited condition, a carrier would be unaffected in the absence of another POLG gene mutation

rs3738579(T;T)
1.5x – 2x increased risk for cervical cancer, HNSCC, and breast cancer

Bad Repute
3 Magnitude
38.1% Frequency
2013-11-07 Geno Modified
0.2392 GMAF
1 Publications
RNASEL Genes
1 Chromosome
182586901 Position
3 Max Magnitude
2018-12-05 Rs Modified
minus Stabilized
minus Orientation

rs3738579 represents a SNP in the 5′ UTR region upstream of the RNASEL gene. A study of patients diagnosed with carcinoma of the uterine cervix, head and neck squamous cell carcinomas (HNSCC), and breast cancer found 1.5x-2x increased risk for all three cancer types for the rs3738579(T;T) genotype, while finding decreased risk (0.5x) for rs3738579(C;T) heterozygotes. rs3738579(C;C) homozygotes had 0.6x less risk for cervical cancer but increased risk for HNSCC (1.4x) and breast cancer (1.8x). Although statistics were not reported per genotype, a combination of data from all three cancer forms over all genotypes provided strong statistical evidence for rs3738579 as a cancer marker, with a p-value of 4.43×10(-5).

Carrier of a biotinidase deficiency mutation Unaffected in absence of another BTD gene mutation; see rs13078881

rs13078881, also known as c.1330G>C, p.Asp444His and D444H, represents a mutation in the BTD gene on chromosome 3. Inherited recessively, the rs13078881(C) allele is considered by ClinVar (and BabySeq) as a pathogenic mutation for biotinidase deficiency. However, it appears as if the D444H mutation results in 48% of normal enzyme activity, and if found in combination with a BTD gene mutation associated with profound deficiency, may result in partial biotinidase deficiency. Note that this condition is treatable; children with biotinidase deficiency identified early enough should remain asymptomatic if biotin therapy is instituted early. Profound biotinidase deficiency in two asymptomatic adults. Partial biotinidase deficiency is usually due to the D444H mutation in the biotinidase gene. Mutations causing profound biotinidase deficiency in children ascertained by newborn screening in the United States occur at different frequencies than in symptomatic children….

 

Bad
3
4.8%
TSIMKKMEXLWKGIHCHDASWYRIJPTHCBCEU012.52537.55062.57587.5100
3
2017-01-15
0.01882
Pathogenic
3
BTD
3
15645186
6.7
2018-12-05
plus
plus

 

risk factor for systemic sclerosis see discussion at rs55687265

rs55687265, also known as c.1308C>G, p.Phe43Leu and F436L, is a rare variant in the ATP8B4 gene on chromosome 15. Exome sequencing followed by a replication cohort study and then a meta-analysis determined that the rs55687265(C) allele, as oriented in dbSNP, is associated with higher risk for systemic sclerosis (SSc; meta-analysis odds ratio 2.5, p = 1.92 x 10e-7).

 

Bad
3
2015-10-19
1
ATP8B4
15
49934162
3
2017-05-05
plus
plus

red hair possible, higher risk of melanoma

rs1805009, known as Asp294His or D294H and located in the MC1R gene, is a variant associated with red hair ( redheads) and low tanning in one study., Reported as i3002507 by 23andMe in January 2015. The risk allele is rs1805009(C), compared with the wild-type rs1805009(G) allele. See also OMIM 155555.0001 blog about designing melanocortin analogs specific to these genotypes.
Bad
3
2
2016-07-13
0.005051
Other
5
MC1R TUBB3
16
89920138
3
2019-01-12
plus
plus

One copy of H63D, carrier of hemochromatosis, likely unaffected unless also C282Y carrier. You are a carrier for rs1799945(G) H63D Hereditary hemochromatosis. You are unlikely to be affected unless also a carrier of rs1800562(A) C282Y, but others in your family may be. This is a treatable condition.

rs1799945, also known as H63D or His63Asp, represents a SNP that accounts for a mild form of hereditary hemochromatosis (HH), an iron overload condition in which mutations of certain genes involved in iron metabolism disrupt the body’s ability to regulate uptake of iron, causing increased intestinal iron absorption. The most common form is caused by mutations in the HFE gene, which are inherited recessively. The gene for HH is closely linked to the HLA-A3 locus on the short arm of chromosome 6. In 1996, HFE, a gene for HH, was found to have two missense mutations. A mutation at amino acid 282 (C282Y) was found to be homozygous in 83 percent of patients with HH. This is a point mutation from guanine to adenine, resulting in a missense mutation from cysteine to tyrosine. Such mutations are commonly found in people with European ancestry, and is more rare in Asian and African populations. Among individuals of northern European descent, hereditary hemochromatosis is the most common inherited identified genetic disorder. However, penetrance differs between different populations….

 

Bad
3
35.6%
2
2012-03-05
0.08356
Other
28
HFE LOC108783645
6
26090951
4
2018-12-06
plus
plus

1.5x increased risk for CAD 1.5x higher risk for coronary artery disease

rs1333049 has been reported in a large study to be associated with heart disease, in particular, coronary artery disease. The risk allele (oriented to the dbSNP entry) is most likely (C); the odds ratio associated with heterozygotes is 1.47 (CI 1.27-1.70), and for homozygotes, 1.9 (CI 1.61-2.24). This SNP has also been reported to have the highest association of any SNP studied in a subsequent experiment conducted with the resources of the German MI [Myocardial Infarction] Family Study. [, ] The initial studies were conducted on Caucasian populations. A subsequent study of Japanese and Korean patients has also found rs1333049 to be associated with increased coronary artery disease risk, with roughly similar odds ratios. Further reading (with comments) – A long-term study of a cohort of 769 individuals finds that the
•Shared genetic susceptibility to ischemic stroke and coronary artery disease: a genome-wide analysis of common variants.
•Genome-wide association study for coronary artery calcification with follow-up in myocardial infarction.
•Two-marker association tests yield new disease associations for coronary artery disease and hypertension.
•A Genome-wide Association Study Identifies LIPA as a Susceptibility Gene for Coronary Artery Disease.
•Genomewide association analysis of coronary artery disease.
•Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls….
Bad
3
50.4%
3
2012-01-09
0.4334
98
9
22125504
4
2019-09-02
plus
plus

 

1.3x higher risk of ER+ breast cancer

rs2981582 in the FGFR2 gene was one of the four strongest associations found in a genome-wide association study ( GWAS) of over 4,000 breast cancer samples. The T allele was more strongly related to ER-positive (per-allele odds ratio 1.31 (CI: 1.27-1.36)) than ER-negative (odds ratio 1.08 (CI:1.03-1.14)) disease (p for heterogeneity = 10(-13)). While on its own still of fairly small effect, this was the most significant of 7 SNPs to help estimate risk of breast cancer. Family history and/or BRCA1 or BRCA2 testing status are more significant factors, which were not part of this panel. Based on a study of 1,049 Chinese breast cancer patients, carriers of risk alleles at three SNPs ( rs2981582, rs1219648 and rs2420946) were at 1.36x increased risk for breast cancer (CI: 1.13-1.62, p = 0.001). A study of 1,173 Caucasian ovarian cancer patients did not find strong support for an association….

 

Bad
3
41.6%
TSIMKKMEXLWKGIHCHDASWYRIJPTHCBCEU012.52537.55062.57587.5100
3
2013-05-14
0.405
75
FGFR2
10
121592803
3.2
2019-04-21
minus
minus

 

1.94x risk of developing rheumatoid arthritis

rs3738919, a SNP located in the ITGAV gene, was identified in a European study to be associated with rheumatoid arthritis (RA). The risk allele for rs3738919 is the more common allele, (C). For the three European Caucasian populations studied (372 RA patients + 330 controls), and combining the (C;C) and (A;C) genotypes in comparison to the (A;A) genotype, the odds ratio for RA = 1.94 (CI: 1.3–2.9, p = 0.002). There was no significant difference in RA risk between those carrying one or two (C) alleles. An editorial about this finding has been published.

 

Bad
2.5
46%
2013-11-07
0.2107
3
ITGAV
2
186656533
2.5
2018-12-05
plus
plus

~20-30x higher risk for Fuchs’ dystrophy, a corneal disorder

rs17595731 is a SNP in the transcription factor 4 TCF4 gene. It is one of several TCF4 SNPs reported to be independently associated with Fuchs’ dystrophy.

Bad
2.5
1.5%
2
2013-12-25
0.04545
1
TCF4
18
55440221
2.5
2015-01-02
plus
plus

 

1.16x increased risk of Osteoarthritis Osteoarthritis

 

 

Bad
2.5
34.5%
3
2014-06-16
0.1864
2
COG5
7
107297975
3
2018-12-06
plus
plus

Substantially increased odds of developing V617F-positive MPN.

23andMe blog At rs12340895(G) (equivalent to rs12343867 in the study) had nearly four times higher odds of developing V617F-positive myelofibrosis (MPN) compared to people without the disease. 23andMe recently replicated this association, though we see a smaller effect— in our database, people with a G at rs12340895 have about two times the odds of developing V617F-positive MPN compared to people without the disease. n A at rs3780374 in the JAK2 gene (equivalent to rs4495487 reported in the study and highly correlated with rs12343867) have about three times higher odds of developing V617F-positive MPN compared to individuals without the A version. The following SNPs are (all) associated with the JAK2 46/1 haplotype that appears to predispose to V617F-positive neoplasms; since they are all part of one haplotype (and are not independent of one another), having one usually implies having the others as well….

 

Bad
2.5
46.9%
2012-08-14
0.2511
INSL6 JAK2
9
5099677
2.8
2017-09-03
plus
plus

 

Increased odds (2 – 4 fold?) of V617F-associated MPNs

The following SNPs are (all) associated with the JAK2 46/1 haplotype that appears to predispose to V617F-positive neoplasms; since they are all part of one haplotype (and are not independent of one another), having one usually implies having the others as well.
• rs12343867
• rs12340895
• rs3780374
• rs4495487
• rs10974944
Bad
2.5
45.1%
3
2014-08-17
0.2567
10
INSL6 JAK2
9
5070831
3
2018-12-06
plus
plus

probably increased risk of breast cancer Due to orientation issues, this snp was problematic, but is not believe to be stabilized correctly.

rs28997576, aka Cys557Ser or C557S, is a missense variant in the BRCA1 associated RING domain 1 BARD1 gene on chromosome 2. Researchers suggest that BARD1 Cys557Ser (rs28997576) is an ancient variant that confers risk of single and multiple primary breast cancers, and this risk is amplified in carriers of the BRCA2 999del5 (codon 257, exon 9) mutation. For just the rs28997576(C;G) individuals, the reported odds ratio was 1.82 (CI: 1.11-3.01, p = 0.014), but if the person also carries a rs80359671 or rs80359675 BRCA2 999del5 variant, the odds ratio was reported as 3.11 (CI: 1.16-8.40, p = 0.046). Family history was associated with (slightly) increased risk. In 300 breast cancer cases in South Americans, rs28997576(C;G) was associated with increased breast cancer risk if, and only if, there was a family history. The odds ratio was 3.4 (CI: 1.2-10, p = 0.04). In families with at least three BC and/or ovarian cancer cases, risk was further increased in the carriers of the…

 

Bad
2.5
2015-01-24
0.007805
Other
4
BARD1
2
214752454
2.5
2018-01-06
minus
minus

 

1.39x increased risk for PCSM in patients with prostate cancer For a person already diagnosed with prostate cancer, this relatively common genotype is associated with a more aggressive form of the cancer and an increased risk (by 1.39x) of dying from causes related to the cancer.

rs11672691 is a SNP on chromosome 19 located between the ATP5SL and CEACAM21 genes and within LOC100505495, a possible noncoding RNA. A large study of over 10,000 patients with prostate cancer concluded that each rs11672691(G) allele was associated with an increased risk (by 1.18x) of prostate cancer specific mortality (PCSM), i.e. death from the cancer. A meta-analysis of 4 studies totaling ~6000 patients with prostate cancer and follow up in 49,000 samples concluded that rs11672691 was associated with increased susceptibility (odds ratio 1.12, CI:1.03–1.21, p = 1.4 x 10e-8) but also with aggressive prostate cancer and therefore a poorer prognosis. A study published in Cell in 2018 suggests that the rs11672691(G) variant acts to increase the transcript levels of PCAT19 and CEACAM21, two proteins associated with cell growth and tumor progression….

 

Bad
2.5
51.3%
2
2014-05-30
0.449
4
PCAT19
19
41479679
2.5
2019-07-28
plus
plus

 

common but 10x higher glaucoma risk in most (but not all) populations This genotype is found in 2 out of 3 people, but has been repeatedly linked to a much higher risk of glaucoma. However a 2010 paper in a south african population reports reduced risk, casting some doubts.

rs3825942, also known as G153D, a SNP causing an amino acid change in the lysyl oxidase 1 LOXL1 gene, has been linked to exfoliation glaucoma (also known as exfoliation syndrome). This form of glaucoma causes up to 10% of the cases of blindness in many countries, including the US. From the abstract of this study: “Approximately 25% of the general population is homozygous for the highest risk haplotype [C;C here combined with other risk SNPs] and their risk of suffering XFG (exfoliation glaucoma) is over 100 times that of those only carrying low-risk haplotypes.” The risk allele for this SNP is rs3825942(C), as oriented with respect to the dbSNP entry, and it confers a estimated relative risk (by itself) of 27 compared to the (T) allele. The odds ratio is 20.10 (CI 10.80-37.41). [Note that the (C) allele is actually quite common in most European populations.] A meta-analysis including 24 articles across 5 ethnicities (Caucasian, African, Japanese, Indian, and Chinese) concluded that…

 

Bad
2.3
68.3%
2
2017-06-19
0.225
Other
48
LOXL1 LOXL1-AS1
15
73927241
2.5
2019-07-03
plus
plus

 

1.38x increased risk for prostate cancer

rs4430796 is a SNP in the TCF2 gene on chromosome 17q12, associated with increased risk for prostate cancer in several studies. In a study of over 3,600 Caucasians with prostate cancer, rs4430796 is one of five SNPs used (with family history as a sixth factor) to cumulatively predict overall risk. On its own, the rs4430796(A;A) risk genotype – in dbSNP orientation, not as published – yields an odds ratio for developing prostate cancer of 1.38 (CI: 1.21-1.57, p=1.6x10e-6) and may account for 10.2% of population attributable risk. article linking to Prostate cancer and type-2 diabetes 403 non-Hispanic white families were studied, totaling 1,015 men, to reach the conclusion that the rs4430796(A) allele is associated with increased prostate cancer risk; the odds ratio was 1.40 (CI: 1.09-1.81) under an additive genetic model. Notably,…

Bad
2.1
19.5%
3
2013-04-21
0.4656
61
HNF1B
17
37738049
2.1
2018-01-06
plus
plus

1.6x major depressive disorder risk

[GWAS:Major depressive disorder]

 

Bad
2.1
15.4%
3
2015-05-25
0.09091
1
LOC105372174 LOC643542
18
67618042
2.1
2019-07-03
plus
plus

 

2x increased risk for esophageal squamous cell cancer among Han Chinese You have a total of 3 or 4 SNP variants (out of 6) associated in Han Chinese with increased risk for esophageal squamous cell cancer, which reportedly places you on average at about double the risk (2x) of developing the disease, if you are of Chinese ancestry. Smoking and alcohol use will apparently increase your risk further.
Bad
2
2011-09-29

 

1.51x increased risk for Alzheimer’s

While the ApoE4 allele ( rs429358(C)) is widely accepted as the predominant genetic risk factor for Alzheimer’s disease, there are likely to be numerous other factors, both genetic and environmental, associated to lesser degrees with susceptibility to the disease. Genes influencing the immune system, and in particular susceptibility to viral infections such as herpes, may be among such factors. This SNP, located in the TAP2 gene and thus implicated in the activation of HIV and HSV-1 viruses, is seen more commonly in ~300 Alzheimer patients than in the same number of controls. The risk allele is rs241448(C). The odds ratio is reported to be 2.14 (CI: 1.02-2.55) for rsrs241448(C;C) homozygotes, and 1.51 (CI: 0.80-1.93) for rsrs241448(C;T) heterozygotes, compared with rsrs241448(T;T) homozygotes. This may be particularly significant for carriers of…

Bad
2
36%
2013-03-24
0.2934
Non-pathogenic
4
TAP2
6
32828908
2.1
2018-12-06
minus
minus

 

Small increase in ALS risk; better lithium response in ALS patients see discussion at rs12608932

rs12608932 is a SNP located in an intron of the UNC13A gene which encodes UNC13A, a protein involved with regulation of neurotransmitters like glutamate at central and neuromuscular synpases. Genome-wide association studies (GWAS) have repeatedly detected a significant but modest association between rs12608932(C) and risk for amyotrophic lateral sclerosis (ALS), with an odds ratio <1.30, but the SNP appears to convey a larger effect on survival in those who actually have ALS. Mean survival in rs12608932(C;C) ALS patients is 6 to 12 months shorter compared those carrying one or two (A) alleles. Approximately 16% of ALS patients are rs12608932(C;C), and a meta-analysis shows that, in contrast to C9orf72-associated ALS patients, treatment with lithium carbonate improved the 12-month survival from 40.1% (CI: 23.2–69.1) to 69.7% (CI: 50.4–96.3).
•Genome-wide association study identifies 19p13.3 (UNC13A) and 9p21.2 as susceptibility loci for sporadic amyotrophic lateral sclerosis…
Bad
2
12.4%
2017-11-17
0.4325
9
UNC13A
19
17641880
2
2018-12-06
plus
plus

 

1.3x increased coronary artery disease risk

rs1333048 increases susceptibility to coronary artery disease 1.30 times for heterozygotes (AC) and 1.54 times for homozygotes (CC) rs1333048 2x risk for periodontitis and a confirmation of coronary heart disease 23andMe blog

 

Bad
2
49.6%
3
2013-06-07
0.4541
9
9
22125348
2.1
2019-01-04
plus
plus

 

1.4x increased risk for heart disease

rs10757274 and rs2383206 can significantly increase the risk of heart disease http://www.sciencemag.org/cgi/content/short/316/5830/1488. About one in every four Caucasians are thought to carry the variants, and their risk of coronary heart disease is increased by 30 to 40%. rs10757278 in the same region has been linked to diabetes http://www.forbes.com/forbeslife/health/feeds/hscout/2007/05/03/hscout604291.html. The chromosomal region where these SNPs are located is 9p21, and has no known genes. a blog post about investigating rs10757274 and rs2383206 This SNP was also associated with increased risk for coronary artery disease in a Korean population. Also found to be significant in a study of 416 Italian myocardial infarction patients. A study of 1,000+ patients with early-onset angiographic…
 
Bad
2
56.9%
2
2012-01-09
0.4917
34
CDKN2B-AS1
9
22115027
3
2019-09-02
plus
plus

 

increased risk for psoriasis

rs1265181 is a SNP in the HLA region of chromosome 6. A large study (>6,000 Chinese psoriasis patients and an equal number of controls) found a highly significant association between the minor rs1265181(G) allele and risk for psoriasis. A proxy for this allele is rs1265159(A). See also: 23andMe blog psoriasis

 

Bad
2
39.1%
TSIMKKMEXLWKGIHCHDASWYRIJPTHCBCEU012.52537.55062.57587.5100
2014-01-06
0.1102
6
6
31188008
2.5
2018-12-06
minus
minus

 

1.6x risk of coronary artery disease

rs6922269 has been reported in a large study to be associated with heart disease, in particular, coronary artery disease. The risk allele (oriented to the dbSNP entry) is (A); the odds ratio associated with heterozygotes is 1.17 (CI 1.04-1.32), and for homozygotes, 1.65 (CI 1.32-2.06).

 

Bad
2
8.3%
2
2016-04-21
0.2906
19
MTHFD1L
6
150931849
2
2018-12-06
plus
plus