Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000486194 | SCV000570292 | uncertain significance | not provided | 2024-03-27 | criteria provided, single submitter | clinical testing | Reported in at least one individual undergoing testing for the BRCA1 and BRCA2 genes (PMID: 23942203); Also known as 8858A>G; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 29884841, 32377563, 35585550, 12228710, 23942203) |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001193173 | SCV001361857 | uncertain significance | not specified | 2019-02-08 | criteria provided, single submitter | clinical testing | Variant summary: BRCA2 c.8630A>G (p.Glu2877Gly) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8.1e-06 in 245760 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.8630A>G has been reported in the literature as part of a validation study (Tarabeux_2014) with no clear phenotypic information being provided. This report does not provide an unequivocal conclusion about association of the variant with Hereditary Breast and Ovarian Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Ambry Genetics | RCV002376878 | SCV002687782 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-02-11 | criteria provided, single submitter | clinical testing | The p.E2877G variant (also known as c.8630A>G), located in coding exon 19 of the BRCA2 gene, results from an A to G substitution at nucleotide position 8630. The glutamic acid at codon 2877 is replaced by glycine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV002525860 | SCV003474885 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2025-02-02 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 2877 of the BRCA2 protein (p.Glu2877Gly). This variant is present in population databases (no rsID available, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 421175). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |