hu3A1B15 - GET-Evidence variant report

Variant report for hu3A1B15

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VariantClinical
Importance
ImpactAllele
freq
Summary
1CBS-I278THighLikelyLikely pathogenic

Recessive, Carrier (Heterozygous)
0.00288158This recessive mutation causes homocystinuria in a recessive manner and is found in patients responsive to pyridoxine treatment.1
2SIAE-M89VModerateUncertainUncertain pathogenic

Recessive, Carrier (Heterozygous)
0.0400632This variant was reported to be associated with autoimmune disease when homozygous. However, a later publication has contradicted this result, finding no significant association between this variant and autoimmune disease in a very large cohort.1
3COL4A1-Q1334HLowLikelyLikely pathogenic

Dominant, Heterozygous
0.324689This common variant has been associated with arterial stiffness and, in Japanese, a small increased risk of myocardial infarction (MI, a.k.a. heart attack). This last observation supported a dominant effect for this variant and, assuming a lifetime risk of 15% for MI, we estimate carriers have an additional risk of 0.5-3%.1
4MTRR-I49MLowLikelyLikely pathogenic

Recessive, Homozygous
0.451199This common variant (HapMap allele frequency of 31.3%) in a protein involved in folate (B9) and cobalamin (B12) metabolism and is often reported as "MTRR I22M" (an alternative transcript position). Mothers homozygous for this variant are associated with having around a increased chance of a child with Down syndrome (risk of 0.4%, average risk in population is 0.25%). Notably, age plays a far larger role in the rate of Down syndrome (risk is 4.5% for a mother 45-years-of-age), and it is unknown how this variant may combine with the effect of age. There are conflicting reports associating this variant with incidence of neural tube defects, possibly when combined with MTHFR A222V.1
5PRF1-A91VLowLikelyLikely pathogenic

Complex/Other, Heterozygous
0.0325339This variant may be associated with a slightly increased susceptibility to some rare blood disorders, in particular autoimmune proliferative disease, if combined with a more severe mutation elsewhere. Most reports lack statistical significance.1
6AMPD1-Q12XLowLikelyLikely pathogenic

Recessive, Carrier (Heterozygous)
0.0930643Causes Adenosine Deaminase Deficiency in a recessive manner. Most of the time individuals do not report symptoms, but when symptoms do exist they to be post-exercise symptoms of muscle weakness, muscle pain, and getting tired more quickly.1
7MBL2-G54DLowLikelyLikely pathogenic

Recessive, Carrier (Heterozygous)
0.103923This variant is associated with mannose binding protein deficiency which leads to impaired complement system immune response to mannose-rich pathogens. Patients homozygous for this allele or compound heterozygous are likely to have increased susceptibility to infection, but Hellemann et al. report heterosis for intensive care outcomes in heterozygous subjects. The wild-type version of this gene is known as variant allele A, while this is called variant allele B. See R52C (variant D) and G57E (variant C).1
8rs5186LowLikelyLikely pathogenic

Unknown, Homozygous
0.214878This common noncoding genetic variant has an allele frequency of ~30% and is associated with an increased risk of hypertension. If ~25% of non-carriers have hypertension, Bonnardeaux et al's data predict ~4% increased risk of hypertension per copy of this variant. This SNP is in the 3' noncoding region of the AGTR1 transcript (angiotensin II type 1 receptor), also known as AT2R1 or AT1R, which is a target of hypertension drugs.1
9RNASEL-R462QLowUncertainUncertain pathogenic

Complex/Other, Heterozygous
0.278026Associated with increased risk of prostate cancer in individuals who already have a family history of prostate cancer, but studies have been unable to replicate this finding in sporadic (non-familial) prostate cancer cases.1
10ELAC2-S217LLowUncertainUncertain pathogenic

Complex/Other, Heterozygous
0.273471Reported to be associated with increased susceptibility to prostate cancer, but later studies weaken the hypothesis. Xu et al.'s meta-analysis concludes that there is a small but significant increased risk (OR = 1.13). Assuming a lifetime risk of 16% for prostate cancer we calculate this leads to an increased risk of ~1.5% (17.5% total).1
11SP110-L425SLowUncertainUncertain pathogenic

Unknown, Homozygous
0.863357This variant is associated with a slightly increased risk of tuberculosis. It is unclear whether it is itself causal, or in linkage disequilibrium with some other causal variant that has a stronger effect.1
12MPO-M251TLowUncertainUncertain pathogenic

Recessive, Carrier (Heterozygous)
0.0091095A single sporadic observation implicated this variant in causing myeloperoxidase (MPO) deficiency in a recessive manner, but lacks any statistical significance. MPO deficiency generally causes no symptoms, but there are reports of associations with some cancers.1
13TP53-P72RLowUncertainUncertain pathogenic

Unknown, Homozygous
0.627743This is a common variant was first reported as a polymorphism. It has since had mixed associations with cancer: Storey et al. conclude a 7x *increased* risk of HPV cancer for homozygotes vs hets, but Jones et al. find a 1.98x *decreased* risk for colorectal cancer. This variant may have significant impact on particular cancers, but it is unclear what effect it has on the overall burden of cancer.1
14WFS1-R611HLowUncertainUncertain not reviewed

Recessive, Carrier (Heterozygous)
0.400446This nonsynonymous SNP is associated with Wolfram Syndrome (known as DIDMOAD), which is characterized by early-onset non-autoimmune diabetes mellitus, diabetes insipidus, optic atrophy, and deafness) and to adult Type Two Diabetes Mellitus. The WFS1 gene maps to chromosome 4p16.3. The variant has been shown to be statistically associated with type II diabetes in six UK studies and one study of Ashkenazi Jews (Sandhu, M., et al., Minton et al.).1
15rs1544410LowUncertainUncertain pharmacogenetic

Unknown, Heterozygous
0.351562rs1544410 is a Vitamin D Receptor (VDR) single nucleotide polymorphism. It is unlikely that it has functional significance because it is located in an intron (Liu et. al.), but it is in strong linkage disequilibrium with rs731236 (Dvornyk et al), which is located in an exon. 1
16PCSK9-R46LModerateLikelyLikely protective

Unknown, Heterozygous
0.0101389This variant is reported to have a dominant protective effect against coronary heart disease. Carriers of this variant have about half the risk of coronary heart disease compared to non-carriers (6.3% risk in carriers vs. 11.8% risk in non-carriers).1
17NPC1-H215RLowLikelyLikely protective

Complex/Other, Heterozygous
0.295687This variant is associated with a reduced risk of obesity, with an additive effect of -0.084 BMI per allele (an average of 0.54 pounds less, per allele, in a 5'6" individual). 1
18TOR1A-D216HLowLikelyLikely protective

Unknown, Heterozygous
0.102993This SNP has been shown to be benign and play a protective role against Dystonia. 1
19KCNJ11-K23ELowLikelyLikely protective

Unknown, Heterozygous
0.738148This variant is associated with decreased risk of type 2 diabetes. It is unclear whether this variant has additive effects, or acts in a dominant or recessive manner. Assuming diabetes has a lifetime risk of 36%, we estimate a decreased risk of around 1-2% per copy of this variant.1
20MTR-D919GLowUncertainUncertain protective

Complex/Other, Heterozygous
0.217234This variant was weakly associated with a protective effect vs. colorectal cancer, but only in individuals with low alcohol consumption. 1
21IRS2-G1057DLowUncertainUncertain protective

Unknown, Heterozygous
0.232615a.k.a Gly1057Asp, insulin receptor substrate-2 IRS2. The rs1805097(G) allele is associated with the Gly, and the (A) allele with Asp. A longevity study concluded that rs1805097(A;A) individuals were about twice as likely to live over 85 y/o (odds ratio 2.03, CI:1.39-2.99, p = .0003). 1
22DMD-R2155WLowLikelyLikely benign

Unknown, Heterozygous
0.0269529Probably benign.1
23PMS2-P470SLowLikelyLikely benign

Unknown, Heterozygous
0.374884Benign, common variant.1
24COL9A2-T246MLowLikelyLikely benign

Unknown, Heterozygous
0.0252835Probably benign.1
25FANCA-M717ILowLikelyLikely benign

Unknown, Heterozygous
0.0216583Rare polymorphism, not considered pathogenic.1
26CACNA1S-L458HLowLikelyLikely benign

Unknown, Heterozygous
0.27282Common polymorphism1
27MLH1-I219VLowUncertainUncertain benign

Dominant, Heterozygous
0.239822Computational evidence, functional assays, and case/control studies suggest this variant is probably benign.1
28GAA-E689KLowUncertainUncertain benign

Complex/Other, Heterozygous
0.0301845This is also known as the GAA*4 allozyme is frequent in the Asian population and appears to have somewhat reduced enzyme activity. Kroos et al. rule out pathogenic effect.1
29TYR-S192YLowUncertainUncertain benign

Unknown, Homozygous
0.270682This variant is reported to affect skin pigmentation. It is associated with lighter skin in South Asians (OR 4-5) and with a lack of freckles in Europeans (OR 1.3).1
30GALT-N314DLowUncertainUncertain benign

Unknown, Heterozygous
0.0716676This variant has an allele frequency of ~8% and is ancestral to "Duarte" / "Duarte 2" and "Duarte 1"/"Los Angeles" galactosemia variants. This variant is evolutionarily ancestral, and in vitro studies fail to support an impact of this variant on enzyme activity. Carney et al. instead implicate a 4 base deletion on the 5' of the GALT gene as being causal and linked to this variant. Galactosemia is typically screened and detected in infants and causes early, severe but nonspecific symptoms (digestive problems, lethargy, failure to thrive).1
31MAPT-Q230RLowUncertainUncertain benign

Unknown, Heterozygous
0.0420019Common polymorphism.1
32PTCH1-P1315LLowUncertainUncertain benign

Unknown, Heterozygous
0.29631Common polymorphism, presumed benign.1
33PKP2-L366PLowUncertainUncertain benign

Unknown, Heterozygous
0.221231This variant is a benign polymorphism. 1
34PCSK9-G670ELowUncertainUncertain benign

Unknown, Homozygous
0.888269This variant is likely benign. 1
35APOB-Y1422CLowUncertainUncertain benign

Unknown, Homozygous
0.999628This position is almost certainly an error in the HG18 reference sequence. 1
36AMPD1-P48LLowUncertainUncertain benign

Unknown, Heterozygous
0.0940695Probably benign, ancestral to15173240 pathogenic Q12X mutation.1
37RP1-N985YLowUncertainUncertain benign

Unknown, Heterozygous
0.348671Probably benign. One report linked this variant to high triglycerides, but a later paper found a nearby SNP with similar association and suggests that both findings are caused by linkage to an undiscovered causal variant.1
38TAS2R38-A49PLowUncertainUncertain benign

Unknown, Heterozygous
0.431121This variant is strongly associated with causing the "taster" phenotype of phenylthiocarbamine (PTC) in a dominant manner.1
39TAS2R38-I296VLowUncertainUncertain benign

Unknown, Heterozygous
0.463376This variant is associated with "taster" status of PTC, along with 49P and 262A. Due to linkage disequilibrium, the independent effects of positions 296 and 262 is unclear. The presence of 49P confers taster status in a dominant fashion, but in the absence of 49P, the presence of 262A/296V is still positively associated with tasting PTC.1
40SLC45A2-L374FLowUncertainUncertain benign

Unknown, Homozygous
0.691764Pigmentation allele for non-black hair, and consequently, possible increased susceptibility to malignant melanoma.1
41TPCN2-G734ELowUncertainUncertain benign

Unknown, Heterozygous
0.286166Pigmentation allele.1
VariantPrioritization scoreAllele
freq
Num of
articles
Zygosity and Prioritization Score Reasons

Gene search

"GENE" or "GENE A123C":

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