hu87BAAD - GET-Evidence variant report

Variant report for hu87BAAD

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VariantClinical
Importance
ImpactAllele
freq
Summary
1PRPH-D141YHighUncertainUncertain pathogenic

Recessive, Carrier (Heterozygous)
0.00365206Hypothesized to cause ALS (or increased susceptibility) in a recessive manner, but this is based on a single observation and may lack statistical significance. The mutant protein appears to form abnormal aggregates.1
2WNT10A-F228IModerateWell-establishedWell-established pathogenic

Unknown, Heterozygous
0.0187907Causes ectodermal dysplasia in a recessive manner (malformations of teeth and nails, abnormal/loss of sweating). Although reports have high statistical significance, allele frequency for this variant is high relative to the incidence of the disease. This suggests it may be milder than other pathogenic variants and cause disease with less than 100% penetrance and/or that the disease is more common than reported. Bohring et al. report heterozygotes for pathogenic variants in this gene often have milder skin, tooth, and nail abnormalities, with males having a higher rate of tooth abnormalities.1
3PPARG-P12AModerateUncertainUncertain not reviewed

Unknown, Heterozygous
0.08867821
4rs5186LowLikelyLikely 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
5MTRR-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
6RNASEL-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
7ELAC2-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
8TGIF1-P83ShiftLowUncertainUncertain pathogenic

Complex/Other, Homozygous
0.138889Severe variants in this gene are associated with holoprosencephaly disorders when combined with loss-of-function variants in SHH. Haploinsufficiency was identified in some families with this condition. It is unclear how likely this variant is to occur in combination with an SHH variant, or what phenotypic effect the variant would have on its own.1
9SP110-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
10TP53-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
11WFS1-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
12BRCA2-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
13ELAC2-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
14CPN1-G178DLowUncertainUncertain pathogenic

Recessive, Carrier (Heterozygous)
0.0356014This rare variant (around 1% allele frequency) is hypothesized to cause carboxypeptidase N deficiency in a recessive manner, especially if combined with a more severe variant. However the findings lack statistical sigificance: only a single case study of an affected individual links this variant to causing the disease. There aren’t any follow-up in vitro studies testing whether this variant affects protein function.1
15TPMT-Y240CLowWell-establishedWell-established pharmacogenetic

Complex/Other, Heterozygous
0.0461825Alone, this variant is known as TPMT*3C -- but often, especially in Caucasians, it is found together with another nonsynonymous variant (A154T) to produce the TPMT*3A variant. Both variants are associated with loss of thiopurine methyltransferase (TPMT) activity, although *3C is milder than *3A. Inability to metabolize thiopurine drugs can lead to severe adverse reactions. Heterozygotes may be advised to take a reduced dosage due to reduced metabolism of the drug.1
16ITPA-P32TLowWell-establishedWell-established pharmacogenetic

Recessive, Carrier (Heterozygous)
0.0609779This variant is associated with inosine triphosphate pyrophosphohydrolase deficiency and may be associated with an adverse reaction to thiopurine drugs (which are used as immunosuppressants). Homozygotes have no detectable ITPase activity, individuals compound heterozygous with another less severe mutation also have severely reduced enzyme activity.1
17rs1544410LowUncertainUncertain 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
18PRNP-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
19NPC1-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
20CFH-V62ILowLikelyLikely protective

Complex/Other, Heterozygous
0.391616Associated with a decreased risk for age related macular degeneration (ARMD). Homozygotes for this have a 4-5% decreased attributable risk (3-4% vs. average 8% risk), heterozygotes have slightly lower than average risk (7%). Non-carriers have an increased risk (12-13%). ARMD impairs sharp vision as age progresses. While there is no cure, treatment can slow progression of the disease and environmental factors (smoking and obesity) contribute to higher risk.1
21IL7R-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
22MTR-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
23LPL-S474XLowUncertainUncertain protective

Unknown, Heterozygous
0.0844953This variant actually increases LPL enzyme activity despite creating a termination codon (see Rip J et al). It appears to be a protective variant, associated with lower triglyceride levels--although the effect is quite weak and explains only 0.5-1% of triglyceride variation.1
24ARSA-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
25CACNA1S-L458HLowLikelyLikely benign

Unknown, Heterozygous
0.27282Common polymorphism1
26ADA-K80RLowLikelyLikely benign

Recessive, Carrier (Heterozygous)
0.0635806This variant has a 3.5% allele frequency in 1000 genomes data. Although OMIM links this to disease, the paper they reference uses in vitro data to conclude that this is a functionally neutral polymorphism.1
27PMS2-P470SLowLikelyLikely benign

Unknown, Heterozygous
0.374884Benign, common variant.1
28NEFL-S472ShiftLowLikelyLikely benign

Unknown, Homozygous
Although a frameshift in this gene would be predicted to cause Charcot-Marie Neuropathy, this particular position appears to reflect a single base insertion error/mutation in the reference genome (in other words, normal individuals are always homozygous for a deletion at this position relative to reference). See chr8:24,811,060-24,811,080 annotations on UCSC.1
29OCA2-R305WLowLikelyLikely benign

Unknown, Heterozygous
0.0815207This variant is associated with eye color, as is OCA2 Arg419Gln. Individuals with this variant are more likely to have brown/black eyes (as opposed to blue/gray or green/hazel). Other variants in this gene are associated with oculocutaneous albinism (albinism which involves skin and eyes).1
30APOB-Y1422CLowUncertainUncertain benign

Unknown, Homozygous
0.999628This position is almost certainly an error in the HG18 reference sequence. 1
31ABCC11-G180RLowUncertainUncertain benign

Unknown, Heterozygous
0.0976947This variant is associated with dry type ear wax (a benign trait) in a recessive manner.1
32ERCC6-R1230PLowUncertainUncertain benign

Unknown, Heterozygous
0.0695297Probably benign.1
33FANCA-S1088FLowUncertainUncertain benign

Unknown, Heterozygous
0.0584681Probably benign. One report hypothesized this variant causing Fanconi Anemia, but the allele frequency (3-7%) is high enough to contradict a highly penetrant pathogenic effect. Later authors have concluded this is a polymorphism, not pathogenic.1
34TYR-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
35PTCH1-P1315LLowUncertainUncertain benign

Unknown, Heterozygous
0.29631Common polymorphism, presumed benign.1
36ABCA4-R943QLowUncertainUncertain benign

Unknown, Heterozygous
0.0316044This is a polymorphism in a gene associated with Stargardt disease. Although it has a slight detectable effect in functional study, it is common in control groups and is not believed to have any significant pathogenic effect.1
37PCSK9-G670ELowUncertainUncertain benign

Unknown, Homozygous
0.888269This variant is likely benign. 1
38RAPSN-R58CLowUncertainUncertain benign

Unknown, Heterozygous
0.0778026Reported as non-pathogenic polymorphism. 1
39SLC45A2-L374FLowUncertainUncertain benign

Unknown, Homozygous
0.691764Pigmentation allele for non-black hair, and consequently, possible increased susceptibility to malignant melanoma.1
40PKP2-L366PLowUncertainUncertain benign

Unknown, Heterozygous
0.221231This variant is a benign polymorphism. 1
41TAS2R38-A49PLowUncertainUncertain benign

Unknown, Heterozygous
0.431121This variant is strongly associated with causing the "taster" phenotype of phenylthiocarbamine (PTC) in a dominant manner.1
42TAS2R38-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
43GUCY2D-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
VariantPrioritization scoreAllele
freq
Num of
articles
Zygosity and Prioritization Score Reasons

Gene search

"GENE" or "GENE A123C":

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