ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.6586A>G (p.Lys2196Glu)

dbSNP: rs398122561
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000509744 SCV000608184 uncertain significance Hereditary cancer-predisposing syndrome 2024-07-04 criteria provided, single submitter clinical testing The p.K2196E variant (also known as c.6586A>G), located in coding exon 10 of the BRCA2 gene, results from an A to G substitution at nucleotide position 6586. The lysine at codon 2196 is replaced by glutamic acid, an amino acid with similar properties. This alteration was identified in an individual diagnosed with breast cancer (Sandoval RL et al. PLoS One, 2021 Feb;16:e0247363). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.
Color Diagnostics, LLC DBA Color Health RCV000509744 SCV000912367 uncertain significance Hereditary cancer-predisposing syndrome 2019-05-30 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001857312 SCV002119274 uncertain significance Hereditary breast ovarian cancer syndrome 2022-01-24 criteria provided, single submitter clinical testing 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. 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. ClinVar contains an entry for this variant (Variation ID: 441478). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. 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 2196 of the BRCA2 protein (p.Lys2196Glu).
University of Washington Department of Laboratory Medicine, University of Washington RCV000509744 SCV003847290 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).
Myriad Genetics, Inc. RCV003316661 SCV004018658 likely benign Breast-ovarian cancer, familial, susceptibility to, 2 2023-06-09 criteria provided, single submitter clinical testing This variant is considered likely benign. This variant is strongly associated with less severe personal and family histories of cancer, typical for individuals without pathogenic variants in this gene [PMID: 25085752].

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