Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002378265 | SCV002667821 | uncertain significance | Hereditary cancer-predisposing syndrome | 2015-12-03 | criteria provided, single submitter | clinical testing | The p.Q2345K variant (also known as c.7033C>A), located in coding exon 13 of the BRCA2 gene, results from a C to A substitution at nucleotide position 7033. The glutamine at codon 2345 is replaced by lysine, an amino acid with 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 p.Q2345K remains unclear. |
| Labcorp Genetics |
RCV003530250 | SCV004254446 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-12-08 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with lysine, which is basic and polar, at codon 2345 of the BRCA2 protein (p.Gln2345Lys). 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: 1756801). 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. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV004999719 | SCV005625264 | uncertain significance | not provided | 2024-11-03 | criteria provided, single submitter | clinical testing | The BRCA2 c.7033C>A (p.Gln2345Lys) variant has been reported in the published literature in a cohort of individuals undergoing multigene panel testing and personal and/or family history of cancer (PMID: 31853058 (2020)). This variant 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. |