ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.2551G>A (p.Glu851Lys)

gnomAD frequency: 0.00001  dbSNP: rs398122662
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000766566 SCV000209941 uncertain significance not provided 2023-03-22 criteria provided, single submitter clinical testing Observed in individuals with unspecified cancer history who underwent multi-gene inherited cancer panel testing (Li et al., 2020); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); Also known as 2670G>A; This variant is associated with the following publications: (PMID: 32377563, 31853058, 15343273, 29884841)
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000159874 SCV000602701 uncertain significance not specified 2016-11-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV000575058 SCV000660996 uncertain significance Hereditary cancer-predisposing syndrome 2023-08-26 criteria provided, single submitter clinical testing The p.E851K variant (also known as c.2551G>A), located in coding exon 9 of the BRCA1 gene, results from a G to A substitution at nucleotide position 2551. The glutamic acid at codon 851 is replaced by lysine, an amino acid with similar properties. This amino acid position is highly 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 this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health RCV000575058 SCV000688389 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-04 criteria provided, single submitter clinical testing
Counsyl RCV000077110 SCV000784873 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 1 2017-01-18 criteria provided, single submitter clinical testing
Invitae RCV000800458 SCV000940174 uncertain significance Hereditary breast ovarian cancer syndrome 2022-10-24 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 91593). This missense change has been observed in individual(s) with clinical features of BRCA1-related conditions (PMID: 21520333). This variant is present in population databases (rs398122662, gnomAD 0.003%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 851 of the BRCA1 protein (p.Glu851Lys). 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 BRCA1 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV000575058 SCV003847586 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).
Sharing Clinical Reports Project (SCRP) RCV000077110 SCV000108907 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 1 2012-05-01 no assertion criteria provided clinical testing

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