Submissions for variant NM_000059.4(BRCA2):c.518G>A (p.Gly173Asp)

dbSNP: rs28897702

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000532896	SCV000635432	uncertain significance	Hereditary breast ovarian cancer syndrome	2024-06-18	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 173 of the BRCA2 protein (p.Gly173Asp). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 462369). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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	RCV001185233	SCV001351402	uncertain significance	Hereditary cancer-predisposing syndrome	2019-05-30	criteria provided, single submitter	clinical testing
GeneDx	RCV001775856	SCV002013156	uncertain significance	not provided	2021-03-03	criteria provided, single submitter	clinical testing	Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Also known as 746G>A
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002298650	SCV002598954	uncertain significance	not specified	2022-09-16	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001185233	SCV002641490	uncertain significance	Hereditary cancer-predisposing syndrome	2024-11-20	criteria provided, single submitter	clinical testing	The p.G173D variant (also known as c.518G>A), located in coding exon 6 of the BRCA2 gene, results from a G to A substitution at nucleotide position 518. The glycine at codon 173 is replaced by aspartic acid, 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 tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.