ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.1366G>A (p.Glu456Lys)

dbSNP: rs778142232
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000704282 SCV000833224 uncertain significance Hereditary breast ovarian cancer syndrome 2023-08-25 criteria provided, single submitter clinical testing 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. ClinVar contains an entry for this variant (Variation ID: 580671). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. This variant is present in population databases (rs778142232, gnomAD 0.003%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 456 of the BRCA2 protein (p.Glu456Lys).
Color Diagnostics, LLC DBA Color Health RCV000773074 SCV000906498 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV000773074 SCV002702931 uncertain significance Hereditary cancer-predisposing syndrome 2022-09-28 criteria provided, single submitter clinical testing The p.E456K variant (also known as c.1366G>A), located in coding exon 9 of the BRCA2 gene, results from a G to A substitution at nucleotide position 1366. The glutamic acid at codon 456 is replaced by lysine, an amino acid with similar properties. This amino acid position is conserved. 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV000773074 SCV003850035 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).

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