huEF066A (23) - GET-Evidence variant report

Variant report for huEF066A (23)

Log file: 




VariantClinical
Importance
ImpactAllele
freq
Summary
1APOE-C130RHighWell-establishedWell-established pathogenic

Complex/Other, Heterozygous
0.135392This is generally known as the ApoE4 allele of ApoE and is associated with increased risk of Alzheimer's. 20-25% of individuals are heterozygous for this variant, and 1-2% are homozygous. Data from Khachaturian et al. suggests an average 7% of all individuals developed Alzheimer's by the age of 80; when this is split by ApoE4 status: 10% of ApoE4 heterozygotes (3% increased attributable risk), 40% of ApoE4 homozygotes (33% increased attributable risk), and 5% of non-carriers (2% decreased attributable risk). Notably, their model suggests 70-75% of people would eventually develop Alzheimer's by the age of 100 regardless of ApoE4 genotype (and 25-30% are resistant, regardless of genotype), but that ApoE4 variants shift the disease onset to occur significantly earlier (4 years earlier for heterozygous carriers, 13 years for homozygotes).1
2LPL-N318SModerateUncertainUncertain pathogenic

Dominant, Heterozygous
0.0134783Also called N291S, this variant has been associated with high hypertriglyceridemia. According to data from Wright et al., carriers of this variant may be two to three times more likely to have very high triglyceride levels, although it is unknown what effect this may have on coronary heart disease.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
4RPGRIP1L-A229TLowLikelyLikely pathogenic

Unknown, Heterozygous
0.0561443This variant is generally not considered pathogenic, but when combined with other severe variants it is associated with rare genetic diseases which involve retinal degeneration. Carrying this variant increases the risk of these diseases, but the overall increased risk is very small because the diseases are very rare.1
5rs5186LowLikelyLikely 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
6MTRR-I49MLowLikelyLikely pathogenic

Recessive, Carrier (Heterozygous)
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
7LRP5-A1330VLowUncertainUncertain pathogenic

Complex/Other, Heterozygous
0.110367In a study of a UK population this variant was associated with a small increased risk of osteoporosis and osteoporotic bone fractures, with each copy of the variant presumed to have an additive effect. A study in Chinese young men failed to find an association with peak bone density. 1
8TP53-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
9BRCA2-N372HLowUncertainUncertain pathogenic

Recessive, Carrier (Heterozygous)
0.23656This is a common variant of BRCA2 (HapMap allele frequency of 23%). The variant is weakly associated with an increased chance of breast cancer, and zygosity of the variant is associated with sex of children: male children are more likely to be homozygous for this variant, female children are more likely to be heterozygous.1
10ABCC6-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
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
12IL7R-T244ILowLikelyLikely protective

Unknown, Heterozygous
0.210169The reference genome variant for this allele has been associated with a slight increased risk of multiple sclerosis. Thus, this variant can be treated as a "protective" variant -- carriers of this variant are slightly less likely to have MS. Because the disease is rare and the effect of this variant is not very strong, the absolute decreased risk for carriers of this variant is less than .05% (less than 1 in 2000).1
13KCNJ11-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
14IRS2-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
15ARSA-N350SLowWell-establishedWell-established benign

Unknown, Heterozygous
0.183199This common variant (HapMap 24.1% allele frequency) causes a loss of a glycosylation site (affecting the size of the protein when studied with gel electrophoresis) but does not affect enzyme activity or stability.1
16OCA2-R419QLowLikelyLikely benign

Unknown, Heterozygous
0.0565161This variant is associated with eye color, as is OCA2 R305W. Individuals with this variant are reported to be more likely to have green/hazel eyes as opposed to blue/gray eyes. Other variants in this gene are associated with oculocutaneous albinism (albinism which involves skin and eyes).1
17LOXL1-R141LLowUncertainUncertain benign

Complex/Other, Heterozygous
0.255899Associated with exfoliative glaucoma & syndrome (XFG & XFS) in various populations, but with contradicting results (protective in Caucasians, pathogenic in Japanese). Based on this it seems the variation itself -- although it affects protein structure -- is not itself causing disease. Instead it is likely associated with other nearby causal variants. As such, it is evaluated as benign by GET-Evidence (which focuses on reporting causal variants). See detailed variant report for disease risk associations.1
18TPCN2-G734ELowUncertainUncertain benign

Unknown, Heterozygous
0.286166Pigmentation allele.1
19TYR-S192YLowUncertainUncertain benign

Unknown, Heterozygous
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
20NTRK1-G613VLowUncertainUncertain benign

Unknown, Heterozygous
0.0429448Also called G607V, this variant has been reported as a nonpathogenic polymorphism.1
21PCSK9-G670ELowUncertainUncertain benign

Unknown, Homozygous
0.888269This variant is likely benign. 1
22NEUROD1-P197HLowUncertainUncertain benign

Unknown, Heterozygous
0.0200781Tentatively presumed benign. Other disruptive mutations in this gene have been reported to cause type 2 diabetes in a dominant manner, but this was found in a PGP participant who does not report having the disease.1
23PKP2-L366PLowUncertainUncertain benign

Unknown, Heterozygous
0.221231This variant is a benign polymorphism. 1
24RP1-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
25TAS2R38-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
26SLC45A2-L374FLowUncertainUncertain benign

Unknown, Homozygous
0.691764Pigmentation allele for non-black hair, and consequently, possible increased susceptibility to malignant melanoma.1
27TAS2R38-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":

Log in