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

gnomAD frequency: 0.00001  dbSNP: rs398122662

Total submissions: 9

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, this alteration is predicted to be deleterious by in silico analysis. 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
Labcorp Genetics (formerly Invitae), Labcorp	RCV000800458	SCV000940174	uncertain significance	Hereditary breast ovarian cancer syndrome	2022-10-24	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 BRCA1 protein function. 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).
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).
All of Us Research Program, National Institutes of Health	RCV000077110	SCV004815679	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 1	2023-08-08	criteria provided, single submitter	clinical testing
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