ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.9640A>G (p.Lys3214Glu)

dbSNP: rs1555289810
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000637487 SCV000758948 uncertain significance Hereditary breast ovarian cancer syndrome 2022-12-11 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 3214 of the BRCA2 protein (p.Lys3214Glu). 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: 531286). 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. 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.
Ambry Genetics RCV003162849 SCV003855529 uncertain significance Hereditary cancer-predisposing syndrome 2022-12-07 criteria provided, single submitter clinical testing The p.K3214E variant (also known as c.9640A>G), located in coding exon 25 of the BRCA2 gene, results from an A to G substitution at nucleotide position 9640. The lysine at codon 3214 is replaced by glutamic acid, an amino acid with similar properties. This alteration was identified in an individual diagnosed with breast cancer (Ahmad J et al. Clin Genet, 2012 Dec;82:594-8). 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.

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