Variant report for hu4F8813 (uploaded1)
- Data source: hu4F8813 (uploaded1)
- This report: evidence.pgp-hms.org/genomes?display_genome_id=f58c7b9bd2b2227b171717418b874c05b9c2b3ac&access_token=2e4675734c0b99232f15b000d62d02b3
- Download: source data
- Processing status: processing
- Show debugging info
Log file:
| Row number | Variant | Clinical Importance | Evidence | Impact | Allele freq | Summary | Sufficient |
|---|---|---|---|---|---|---|---|
| 1 | OPTN-M98K | Moderate | Uncertain | Uncertain pathogenic Unknown, Heterozygous | 0.0613497 | This variant was initially reported to be a risk factor for glaucoma, but subsequent reports have failed to find a statistically significant association. It may have a modifier effect, with carriers of the variant having lower intraocular pressure on average -- pressures that might be considered normal in other individuals would be abnormally high for carriers of this variant. | 1 |
| 2 | COL4A1-Q1334H | Low | Likely | Likely pathogenic Dominant, Homozygous | 0.324689 | This 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 |
| 3 | MTRR-I49M | Low | Likely | Likely pathogenic Recessive, Carrier (Heterozygous) | 0.451199 | This 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 |
| 4 | H6PD-R453Q | Low | Uncertain | Uncertain pathogenic Recessive, Homozygous | 0.308886 | This common variant may have a small pathogenic effect by contributing to cortisone reductase deficiency (a rare abnormality) when homozygous and combined with a serious pathogenic variant. The same authors have tested and ruled out a contribution to polycystic ovary syndrome (similar phenotype, more common disease). | 1 |
| 5 | ELAC2-S217L | Low | Uncertain | Uncertain pathogenic Complex/Other, Heterozygous | 0.273471 | Reported 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 |
| 6 | RNASEL-R462Q | Low | Uncertain | Uncertain pathogenic Complex/Other, Homozygous | 0.278026 | Associated 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 |
| 7 | SP110-L425S | Low | Uncertain | Uncertain pathogenic Unknown, Homozygous | 0.863357 | This 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 |
| 8 | TP53-P72R | Low | Uncertain | Uncertain pathogenic Unknown, Homozygous | 0.627743 | This 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 |
| 9 | WFS1-R611H | Low | Uncertain | Uncertain not reviewed Recessive, Carrier (Heterozygous) | 0.400446 | This 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 |
| 10 | DYX1C1-E417X | Low | Uncertain | Uncertain pathogenic Unknown, Heterozygous | 0.20147 | One study reports this variant to be associated with dyslexia. The study group was relatively small and so the results did not have strong significance. If they are representative this variant is associated with a doubled risk for dyslexia, but it is unclear whether the effect would be additive, dominant, or recessive. | 1 |
| 11 | BRCA2-N372H | Low | Uncertain | Uncertain pathogenic Recessive, Carrier (Heterozygous) | 0.23656 | This 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 |
| 12 | DPYD-M166V | High | Likely | Likely pharmacogenetic Unknown, Heterozygous | 0.0778955 | Associated with DPYD deficiency and poor prognosis for chemotherapy w/ 5-flurorouracil. | 1 |
| 13 | CYP2C9-R144C | Moderate | Well-established | Well-established pharmacogenetic Unknown, Heterozygous | 0.0970982 | This variant, also called CYP2C9*2, is a pharmacogenetic variant that modulates sensitivity for Warfarin (due to reduced metabolism). This variant is associated with Caucasians. The FDA has approved reduced recommended Warfarin dosage based on the presence of this variant. | 1 |
| 14 | ABCC6-R1268Q | Low | Uncertain | Uncertain pharmacogenetic Unknown, Heterozygous | 0.218907 | This 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 |
| 15 | rs1544410 | Low | Uncertain | Uncertain pharmacogenetic Unknown, Homozygous | 0.351562 | rs1544410 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 |
| 16 | FUT2-W154X | Moderate | Well-established | Well-established protective Recessive, Carrier (Heterozygous) | 0.490519 | This 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 |
| 17 | PRNP-M129V | Low | Well-established | Well-established protective Complex/Other, Homozygous | 0.339561 | This 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 |
| 18 | NPC1-H215R | Low | Likely | Likely protective Complex/Other, Heterozygous | 0.295687 | This 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 |
| 19 | IL7R-T244I | Low | Likely | Likely protective Unknown, Heterozygous | 0.210169 | The 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 |
| 20 | KCNJ11-K23E | Low | Likely | Likely protective Unknown, Homozygous | 0.738148 | This 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 |
| 21 | TOR1A-D216H | Low | Likely | Likely protective Unknown, Heterozygous | 0.102993 | This SNP has been shown to be benign and play a protective role against Dystonia. | 1 |
| 22 | MTR-D919G | Low | Uncertain | Uncertain protective Complex/Other, Heterozygous | 0.217234 | This variant was weakly associated with a protective effect vs. colorectal cancer, but only in individuals with low alcohol consumption. | 1 |
| 23 | BRCA2-T1915M | Low | Uncertain | Uncertain protective Unknown, Heterozygous | 0.0205429 | Serrano-Fernández et al. found this variant to be associated with a modest (OR = 1.61) but significant (P = 0.0007) reduction in breast cancer risk. | 1 |
| 24 | MLH1-I219V | Low | Uncertain | Uncertain benign Dominant, Homozygous | 0.239822 | Computational evidence, functional assays, and case/control studies suggest this variant is probably benign. | 1 |
| 25 | RPGRIP1-A547S | Low | Uncertain | Uncertain benign Complex/Other, Heterozygous | 0.232202 | Probably 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 |
| 26 | TAS2R38-A49P | Low | Uncertain | Uncertain benign Unknown, Homozygous | 0.431121 | This variant is strongly associated with causing the "taster" phenotype of phenylthiocarbamine (PTC) in a dominant manner. | 1 |
| 27 | GJB3-R32W | Low | Uncertain | Uncertain benign Unknown, Heterozygous | 0.022309 | Probably benign. Although Polyphen 2 predicts it be damaging and some publications suggested it might have a functional effect, others report it to be a fairly common polymorphism and functional studies failed to find a difference between it and wild type. | 1 |
| 28 | TYR-S192Y | Low | Uncertain | Uncertain benign Unknown, Heterozygous | 0.270682 | This 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 |
| 29 | APOB-Y1422C | Low | Uncertain | Uncertain benign Unknown, Homozygous | 0.999628 | This position is almost certainly an error in the HG18 reference sequence. | 1 |
| 30 | TAS2R38-I296V | Low | Uncertain | Uncertain benign Unknown, Homozygous | 0.463376 | This 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 |
| 31 | NEUROD1-P197H | Low | Uncertain | Uncertain benign Unknown, Heterozygous | 0.0200781 | Tentatively 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 |
| 32 | FANCA-S1088F | Low | Uncertain | Uncertain benign Unknown, Heterozygous | 0.0584681 | Probably 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 |
| 33 | F5-M413T | Low | Uncertain | Uncertain benign Unknown, Heterozygous | 0.0580963 | Presumed benign. This variant is not particularly rare and has not been reported to cause disease. | 1 |
| 34 | F5-D2222G | Low | Uncertain | Uncertain benign Unknown, Heterozygous | 0.0448968 | Other mutations in this gene are associated with Factor 5 deficiency. There is no literature implicating this variant, however, and it is fairly common in the population (3.8% in HapMap), and so it is currently labeled as benign. | 1 |
| 35 | KRT85-R78H | Low | Uncertain | Uncertain benign Recessive, Carrier (Heterozygous) | 0.042466 | Presumed 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 |
| 36 | PCSK9-G670E | Low | Uncertain | Uncertain benign Unknown, Homozygous | 0.888269 | This variant is likely benign. | 1 |
| 37 | RP1-N985Y | Low | Uncertain | Uncertain benign Unknown, Homozygous | 0.348671 | Probably 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 |
| 38 | PKP2-L366P | Low | Uncertain | Uncertain benign Unknown, Heterozygous | 0.221231 | This variant is a benign polymorphism. | 1 |
| 39 | SLC45A2-L374F | Low | Uncertain | Uncertain benign Unknown, Homozygous | 0.691764 | Pigmentation allele for non-black hair, and consequently, possible increased susceptibility to malignant melanoma. | 1 |
| Row number | Variant | Prioritization score | Allele freq | Num of articles | Zygosity and Prioritization Score Reasons | Sufficient |
|---|