ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.2594A>G (p.Glu865Gly)

dbSNP: rs1593897302
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001015891 SCV001176779 uncertain significance Hereditary cancer-predisposing syndrome 2020-07-10 criteria provided, single submitter clinical testing The p.E865G variant (also known as c.2594A>G), located in coding exon 10 of the BRCA2 gene, results from an A to G substitution at nucleotide position 2594. The glutamic acid at codon 865 is replaced by glycine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001234291 SCV001406929 uncertain significance Hereditary breast ovarian cancer syndrome 2021-06-05 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with BRCA2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with glycine at codon 865 of the BRCA2 protein (p.Glu865Gly). The glutamic acid residue is moderately conserved and there is a moderate physicochemical difference between glutamic acid and glycine.
University of Washington Department of Laboratory Medicine, University of Washington RCV001015891 SCV003848433 likely benign Hereditary cancer-predisposing syndrome 2023-03-23 criteria provided, single submitter curation Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
All of Us Research Program, National Institutes of Health RCV004004553 SCV004842806 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2024-02-05 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with glycine at codon 865 of the BRCA2 protein. Computational prediction suggests that this variant may not impact protein structure and function. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with BRCA2-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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