Submissions for variant NM_000059.4(BRCA2):c.5312G>T (p.Gly1771Val)

dbSNP: rs80358755

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000228622	SCV000283260	uncertain significance	Hereditary breast ovarian cancer syndrome	2024-04-10	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1771 of the BRCA2 protein (p.Gly1771Val). This variant is present in population databases (no rsID available, gnomAD 0.006%). This missense change has been observed in individual(s) with breast cancer (PMID: 31706072). ClinVar contains an entry for this variant (Variation ID: 236879). 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.
Color Diagnostics, LLC DBA Color Health	RCV000580812	SCV000683695	uncertain significance	Hereditary cancer-predisposing syndrome	2019-05-05	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000580812	SCV001185849	uncertain significance	Hereditary cancer-predisposing syndrome	2022-05-05	criteria provided, single submitter	clinical testing	The p.G1771V variant (also known as c.5312G>T), located in coding exon 10 of the BRCA2 gene, results from a G to T substitution at nucleotide position 5312. The glycine at codon 1771 is replaced by valine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. 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	RCV000580812	SCV003847157	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).
GeneDx	RCV004591081	SCV005080034	uncertain significance	not provided	2023-12-06	criteria provided, single submitter	clinical testing	Identified in patients with breast cancer (PMID: 31706072); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Also known as 5540G>T; This variant is associated with the following publications: (PMID: 31706072)
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research	RCV000735563	SCV000863701	uncertain significance	Breast and/or ovarian cancer	2015-10-15	no assertion criteria provided	clinical testing