Variant report for hu84082F (23andMe 500K data)
- Data source: hu84082F (23andMe 500K data)
- This report: evidence.pgp-hms.org/genomes?display_genome_id=86ac01e8deb97160369b5f9bec97906e625f09b6&access_token=d38378510375e9afc515be9e919909fb
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| Row number | Variant | Clinical Importance | Evidence | Impact | Allele freq | Summary | Sufficient |
|---|---|---|---|---|---|---|---|
| 1 | COL4A1-Q1334H | Low | Likely | Likely pathogenic Dominant, Heterozygous | 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 | 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 |
| 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 | 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 | MBL2-R52C | Low | Likely | Likely pathogenic Recessive, Carrier (Heterozygous) | 0.048615 | 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 D. See G54D (variant B) and G57E (variant C). | 1 |
| 6 | WFS1-R611H | Low | Uncertain | Uncertain not reviewed Recessive, Homozygous | 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 |
| 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, Heterozygous | 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 | ERCC6-R1213G | Low | Uncertain | Uncertain pathogenic Recessive, Carrier (Heterozygous) | 0.196877 | When homozygous, this variant may cause Cockayne Syndrome, which is a severe autosomal-recessive disorder characterized by abnormal early growth and development, abnormal sensitivity to sunlight, and premature aging. Cockayne Syndrome Type I and Type II lead to death in early childhood. Several other variants in the ERCC6 gene are linked to Cockayne Syndrome. This variant may also be linked to age-related macular degeneration like other ERCC6 variants, and has been linked to colorectal cancer in one study. | 1 |
| 10 | 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 |
| 11 | ITPA-P32T | Low | Well-established | Well-established pharmacogenetic Recessive, Carrier (Heterozygous) | 0.0609779 | This 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 |
| 12 | PECAM1-L125V | Low | Likely | Likely pharmacogenetic Complex/Other, Homozygous | 0.570312 | Mismatched genotypes in this variant between donor and recipient is associated with causing graft vs. host disease in bone marrow transplants. | 1 |
| 13 | rs1544410 | Low | Uncertain | Uncertain pharmacogenetic Unknown, Heterozygous | 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 |
| 14 | FUT2-W154X | Moderate | Well-established | Well-established protective Recessive, Homozygous | 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 |
| 15 | PRNP-M129V | Low | Well-established | Well-established protective Complex/Other, Heterozygous | 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 |
| 16 | CFH-V62I | Low | Likely | Likely protective Complex/Other, Heterozygous | 0.391616 | Associated 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 |
| 17 | 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 |
| 18 | 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 |
| 19 | ABCG5-R50C | Low | Likely | Likely protective Unknown, Homozygous | 0.0684142 | This variant has a mild protective effect on blood cholesterol. It is associated with slightly lower total and LDL cholesterol levels. | 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 | 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 |
| 22 | LIG4-A3V | Low | Uncertain | Uncertain protective Dominant, Heterozygous | 0.035843 | One report has associated this with a decreased risk of multiple myeloma. | 1 |
| 23 | OCA2-R305W | Low | Likely | Likely benign Unknown, Heterozygous | 0.0815207 | This 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 |
| 24 | SLC45A2-E272K | Low | Likely | Likely benign Unknown, Heterozygous | 0.0290946 | Pigmentation allele for black hair in Caucasian population. | 1 |
| 25 | 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 |
| 26 | TPCN2-G734E | Low | Uncertain | Uncertain benign Unknown, Heterozygous | 0.286166 | Pigmentation allele. | 1 |
| 27 | FAH-R341W | Low | Uncertain | Uncertain benign Recessive, Carrier (Heterozygous) | 0.0172895 | This variant shows pseudodeficiency for production of FAH protein which is connected with hereditary tyrosinemia type I. Pseudodeficiency was confirmed with site-directed mutagenesis and expression in a rabbit reticulocyte lysate system. The allelic frequency in 516 Norwegian controls was 0.022. | 1 |
| 28 | 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 |
| 29 | 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 |
| 30 | FMO3-V257M | Low | Uncertain | Uncertain benign Unknown, Heterozygous | 0.0570738 | This common variant (HapMap allele frequency of 9.2%) appears to have no functional effect. OMIM has recorded it as having been seen homozygously in an individual with Trimethylaminuria, but Treacy et al. 1998 conclude it is a polymorphism. | 1 |
| 31 | 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 |
| 32 | 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 |
| 33 | SLC45A2-L374F | Low | Uncertain | Uncertain benign Unknown, Heterozygous | 0.691764 | Pigmentation allele for non-black hair, and consequently, possible increased susceptibility to malignant melanoma. | 1 |
| 34 | 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 |
| 35 | PPOX-P256R | Low | Uncertain | Uncertain benign Recessive, Carrier (Heterozygous) | 0.00725177 | This variant has 0.7% allele frequency in HapMap and occurs in a heme biosynthesis gene. Other variants in this gene are implicated in causing porphyria in a recessive manner, but this variant is considered a polymorphism and retains normal function in a eukaryotic expression system. | 1 |
| 36 | PCSK9-G670E | Low | Uncertain | Uncertain benign Unknown, Homozygous | 0.888269 | This variant is likely benign. | 1 |
| Row number | Variant | Prioritization score | Allele freq | Num of articles | Zygosity and Prioritization Score Reasons | Sufficient |
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