ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.7919A>G (p.Lys2640Arg)

dbSNP: rs397507394
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000773429 SCV000907123 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-28 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001368345 SCV001564738 uncertain significance Hereditary breast ovarian cancer syndrome 2023-12-22 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 2640 of the BRCA2 protein (p.Lys2640Arg). This variant is not present in population databases (gnomAD no frequency). 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: 628766). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA2 protein function with a negative predictive value of 95%. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001800873 SCV002046785 uncertain significance not provided 2021-03-25 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002271584 SCV002556173 uncertain significance not specified 2022-06-25 criteria provided, single submitter clinical testing
Ambry Genetics RCV000773429 SCV002677021 uncertain significance Hereditary cancer-predisposing syndrome 2020-10-09 criteria provided, single submitter clinical testing The p.K2640R variant (also known as c.7919A>G), located in coding exon 16 of the BRCA2 gene, results from an A to G substitution at nucleotide position 7919. The lysine at codon 2640 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is not 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.

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