hu0515BA (ttam v3) - GET-Evidence variant report

Variant report for hu0515BA (ttam v3)

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VariantClinical
Importance
ImpactAllele
freq
Summary
1COL4A1-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
2rs5186LowLikelyLikely pathogenic

Unknown, Heterozygous
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
3ELAC2-S217LLowUncertainUncertain pathogenic

Complex/Other, Homozygous
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
4TP53-P72RLowUncertainUncertain pathogenic

Unknown, Heterozygous
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
5SP110-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
6WFS1-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
7ELAC2-A541TLowUncertainUncertain pathogenic

Unknown, Heterozygous
0.0276074This variant is implicated as causing increased susceptibility to prostate cancer. However the variant has always been seen paired with S217L, it is unclear which variant is causal. Evidence is weak for both; one meta-analysis (Severi et al.) concluded that neither variant was pathogenic, a more recent meta-analysis (Xu et al.) found the data to be significant but the odds ratio was not strong and concluded they are "low-penetrance susceptibility markers of prostate cancer".1
8DPYD-M166VHighLikelyLikely pharmacogenetic

Unknown, Heterozygous
0.0778955Associated with DPYD deficiency and poor prognosis for chemotherapy w/ 5-flurorouracil. 1
9ABCC6-R1268QLowUncertainUncertain pharmacogenetic

Unknown, Heterozygous
0.218907This common polymorphism appears to not have a significant phenotypic impact. A few studies report weak but significant associations with plasma lipids (in Inuits) and thalidomide toxicity.1
10rs1544410LowUncertainUncertain 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
11FUT2-W154XModerateWell-establishedWell-established protective

Recessive, Carrier (Heterozygous)
0.490519This recessive protective variant confers resistance to norovirus (which causes stomach flu). 20% of Caucasians and Africans are homozygous for this variant and are "non-secretors": they do not express ABO blood type antigens in their saliva or mucosal surfaces. Most strains of norovirus bind to these antigens in the gut, and so this non-secretor status confers almost total resistantance to most types of norovirus. There are notable exceptions, some strains of norovirus bind a different target and are equally infectious for secretors and non-secretors.1
12PRNP-M129VLowWell-establishedWell-established protective

Complex/Other, Heterozygous
0.339561This variant is associated with some protective effects for prion disease -- individuals homozygous for this variant are less susceptible to Creutzfeldt-Jakob, and Papua New Guinea individuals heterozygotes at this site are less susceptible to kuru. 1
13NPC1-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
14TOR1A-D216HLowLikelyLikely protective

Unknown, Heterozygous
0.102993This SNP has been shown to be benign and play a protective role against Dystonia. 1
15KCNJ11-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
16TYR-R402QLowWell-establishedWell-established benign

Complex/Other, Heterozygous
0.204964This is a frequent pigmentation polymorphism in Europeans that affects function of the Tyrosinase gene. It is associated with blue instead of green eyes and sun sensitivity. For the most part this variant is benign, but many individuals with ocular albinism (which affects only the eyes) carry this variant along with another more severe variant in the same gene.1
17MLH1-I219VLowUncertainUncertain benign

Dominant, Heterozygous
0.239822Computational evidence, functional assays, and case/control studies suggest this variant is probably benign.1
18RPGRIP1-A547SLowUncertainUncertain benign

Complex/Other, Homozygous
0.232202Probably benign. Implicated in causing autosomal recessive cone-rod dystrophy, but a later report found the same incidence in controls and concludes it is not causal.1
19PCSK9-G670ELowUncertainUncertain benign

Unknown, Heterozygous
0.888269This variant is likely benign. 1
20KRT85-R78HLowUncertainUncertain benign

Recessive, Carrier (Heterozygous)
0.042466Presumed benign. Although this variant was implicated in causing ectodermal dysplasia in a recessive manner in two Pakistani families (one of which was large and consanguineous), GET-Evidence reports that the variant has been seen in 5 out of 114 random control chromosomes. This strongly contradicts a severe pathogenic effect.1
21GUCY2D-A52SLowUncertainUncertain benign

Recessive, Carrier (Heterozygous)
0.21016One publication suggested that this variant possibly causes Leber's congenital amaurosis in a recessive manner, but the frequency data (36% in 1000 genomes) contradicts any significant pathogenic effect.1
22APOB-Y1422CLowUncertainUncertain benign

Unknown, Homozygous
0.999628This position is almost certainly an error in the HG18 reference sequence. 1
23USH2A-V230MLowUncertainUncertain benign

Recessive, Carrier (Heterozygous)
0.0157092This rare variant may be associated with Usher Syndrome II, but the literature seems to have concluded that it is a non-pathogenic polymorphism (including authors who earlier reported it as pathogenic).1
24RP1-N985YLowUncertainUncertain benign

Unknown, Homozygous
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
25TCIRG1-R56WLowUncertainUncertain benign

Unknown, Heterozygous
0.0441778Probably benign. One publication implicates the variant in causing osteopetrosis, but this is contradicted by the relatively high allele frequency for the variant in Caucasians (5%, 1 in 400 homozygous) while that disease is extremely rare (1 in 250,000).1
26TAS2R38-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
27SLC45A2-L374FLowUncertainUncertain benign

Unknown, Heterozygous
0.691764Pigmentation allele for non-black hair, and consequently, possible increased susceptibility to malignant melanoma.1
28TPCN2-G734ELowUncertainUncertain benign

Unknown, Heterozygous
0.286166Pigmentation allele.1
29TAS2R38-A49PLowUncertainUncertain benign

Unknown, Heterozygous
0.431121This variant is strongly associated with causing the "taster" phenotype of phenylthiocarbamine (PTC) in a dominant manner.1
VariantPrioritization scoreAllele
freq
Num of
articles
Zygosity and Prioritization Score Reasons

Gene search

"GENE" or "GENE A123C":

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