Variant report for hu686728 (23andme)
- Data source: hu686728 (23andme)
- This report: evidence.pgp-hms.org/genomes?display_genome_id=d9468dd5857d5e2d39403b9bf0028acaa78cedd6&access_token=8d9bb42b86e05b043ed9603bd79ae506
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| Row number | Variant | Clinical Importance | Evidence | Impact | Allele freq | Summary | Sufficient |
|---|---|---|---|---|---|---|---|
| 1 | 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 |
| 2 | MTRR-I49M | Low | Likely | Likely pathogenic Recessive, Homozygous | 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 |
| 3 | AMPD1-Q12X | Low | Likely | Likely pathogenic Recessive, Carrier (Heterozygous) | 0.0930643 | Causes 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 |
| 4 | MBL2-G54D | Low | Likely | Likely pathogenic Recessive, Carrier (Heterozygous) | 0.103923 | This 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 |
| 5 | rs5186 | Low | Likely | Likely pathogenic Unknown, Heterozygous | 0.214878 | This 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 |
| 6 | 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 |
| 7 | RNASEL-R462Q | Low | Uncertain | Uncertain pathogenic Complex/Other, Heterozygous | 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 |
| 8 | LRP5-A1330V | Low | Uncertain | Uncertain pathogenic Complex/Other, Heterozygous | 0.110367 | In 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 |
| 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 | 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 |
| 11 | 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 |
| 12 | 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 |
| 13 | 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 |
| 14 | H6PD-R453Q | Low | Uncertain | Uncertain pathogenic Recessive, Carrier (Heterozygous) | 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 |
| 15 | DPYD-M166V | High | Likely | Likely pharmacogenetic Unknown, Heterozygous | 0.0778955 | Associated with DPYD deficiency and poor prognosis for chemotherapy w/ 5-flurorouracil. | 1 |
| 16 | TPMT-Y240C | Low | Well-established | Well-established pharmacogenetic Complex/Other, Heterozygous | 0.0461825 | Alone, 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 |
| 17 | TPMT-A154T | Low | Likely | Likely pharmacogenetic Recessive, Carrier (Heterozygous) | 0.0280774 | Usually this variant is found in combination Y240C, forming the TPMT*3A variant. When alone, this variant produces the *3B variant. Both variants are associated with loss of thiopurine methyltransferase (TPMT) activity. 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 |
| 18 | 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 |
| 19 | 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 |
| 20 | KCNJ11-K23E | Low | Likely | Likely protective Unknown, Heterozygous | 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 | 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 |
| 22 | ARSA-N350S | Low | Well-established | Well-established benign Unknown, Heterozygous | 0.183199 | This 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 |
| 23 | ADA-D8N | Low | Likely | Likely benign Dominant, Heterozygous | 0.0295359 | This common variant is reported to reduce adenosine deaminase enzyme activity. It has been associated with an increased tendency for non-REM sleep -- more slow wave sleep, less nocturnal wakings, and a stronger negative impact of sleep deprivation. A role for this gene and variant was previously proposed for autism susceptibility, but this is controversial and was not replicated by later studies. | 1 |
| 24 | SLC45A2-E272K | Low | Likely | Likely benign Unknown, Heterozygous | 0.0290946 | Pigmentation allele for black hair in Caucasian population. | 1 |
| 25 | EFHC1-R182H | Low | Likely | Likely benign Unknown, Heterozygous | 0.0439673 | Probably benign. OMIM appears to incorrectly interpret literature as linking this variant to juvenile myoclonic epilepsy; the authors report it as a polymorphism. | 1 |
| 26 | ADA-K80R | Low | Likely | Likely benign Recessive, Carrier (Heterozygous) | 0.0635806 | This 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 |
| 27 | MLH1-I219V | Low | Uncertain | Uncertain benign Dominant, Heterozygous | 0.239822 | Computational evidence, functional assays, and case/control studies suggest this variant is probably benign. | 1 |
| 28 | LOXL1-R141L | Low | Uncertain | Uncertain benign Complex/Other, Heterozygous | 0.255899 | Associated 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 |
| 29 | PTCH1-P1315L | Low | Uncertain | Uncertain benign Unknown, Heterozygous | 0.29631 | Common polymorphism, presumed benign. | 1 |
| 30 | RP1-N985Y | Low | Uncertain | Uncertain benign Unknown, Heterozygous | 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 |
| 31 | APOB-Y1422C | Low | Uncertain | Uncertain benign Unknown, Homozygous | 0.999628 | This position is almost certainly an error in the HG18 reference sequence. | 1 |
| 32 | AMPD1-P48L | Low | Uncertain | Uncertain benign Unknown, Heterozygous | 0.0940695 | Probably benign, ancestral to15173240 pathogenic Q12X mutation. | 1 |
| 33 | PKP2-L366P | Low | Uncertain | Uncertain benign Unknown, Heterozygous | 0.221231 | This variant is a benign polymorphism. | 1 |
| 34 | HR-T1022A | Low | Uncertain | Uncertain benign Recessive, Carrier (Heterozygous) | 0.0969511 | Probably benign. One study implicated it in causing alopecia universalis, but a later report noted the variant has an allele frequency inconsistent with the rarity of that disease. | 1 |
| 35 | 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 |
| 36 | TAS2R38-A49P | Low | Uncertain | Uncertain benign Unknown, Heterozygous | 0.431121 | This variant is strongly associated with causing the "taster" phenotype of phenylthiocarbamine (PTC) in a dominant manner. | 1 |
| 37 | PCSK9-G670E | Low | Uncertain | Uncertain benign Unknown, Homozygous | 0.888269 | This variant is likely benign. | 1 |
| 38 | 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 |
| 39 | TPCN2-G734E | Low | Uncertain | Uncertain benign Unknown, Heterozygous | 0.286166 | Pigmentation allele. | 1 |
| 40 | TAS2R38-I296V | Low | Uncertain | Uncertain benign Unknown, Heterozygous | 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 |
| Row number | Variant | Prioritization score | Allele freq | Num of articles | Zygosity and Prioritization Score Reasons | Sufficient |
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