ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.7343A>G (p.Lys2448Arg)

dbSNP: rs431825353
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000082972 SCV000785391 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2017-08-02 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000773096 SCV000906551 uncertain significance Hereditary cancer-predisposing syndrome 2022-02-15 criteria provided, single submitter clinical testing This missense variant replaces lysine with arginine at codon 2448 of the BRCA2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001057129 SCV001221605 uncertain significance Hereditary breast ovarian cancer syndrome 2024-04-22 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 2448 of the BRCA2 protein (p.Lys2448Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of BRCA2-related conditions (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 96851). 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%. 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 RCV000773096 SCV002670380 uncertain significance Hereditary cancer-predisposing syndrome 2024-10-24 criteria provided, single submitter clinical testing The p.K2448R variant (also known as c.7343A>G), located in coding exon 13 of the BRCA2 gene, results from an A to G substitution at nucleotide position 7343. The lysine at codon 2448 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is poorly 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.
Baylor Genetics RCV003460760 SCV004216108 uncertain significance Familial cancer of breast 2023-05-26 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV004998219 SCV005625280 uncertain significance not provided 2024-09-09 criteria provided, single submitter clinical testing The BRCA2 c.7343A>G (p.Lys2448Arg) variant has not been reported in individuals with BRCA2-related conditions in the published literature. It also has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.
Sharing Clinical Reports Project (SCRP) RCV000082972 SCV000115046 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2012-05-01 no assertion criteria provided clinical testing

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