Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000960559 | SCV001107551 | benign | not provided | 2025-02-02 | criteria provided, single submitter | clinical testing | |
| Genetic Services Laboratory, |
RCV001819027 | SCV002070908 | benign | not specified | 2021-01-04 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002416232 | SCV002718893 | benign | Cardiovascular phenotype | 2020-01-24 | criteria provided, single submitter | clinical testing | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Gene |
RCV000960559 | SCV003842600 | likely benign | not provided | 2020-10-01 | criteria provided, single submitter | clinical testing | See Variant Classification Assertion Criteria. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001819027 | SCV004039552 | likely benign | not specified | 2023-08-15 | criteria provided, single submitter | clinical testing | Variant summary: ABCG8 c.1963A>G (p.Met655Val) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0014 in 251410 control chromosomes, predominantly at a frequency of 0.019 within the African or African-American subpopulation in the gnomAD database, including 6 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 4 fold of the estimated maximal expected allele frequency for a pathogenic variant in ABCG8 causing Early Onset Coronary Artery Disease phenotype (0.005), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.1963A>G in individuals affected with Early Onset Coronary Artery Disease and no experimental evidence demonstrating its impact on protein function have been reported. Four submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as likely benign. |