Submissions for variant NM_000059.4(BRCA2):c.4586G>C (p.Gly1529Ala)

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002342241	SCV002637477	uncertain significance	Hereditary cancer-predisposing syndrome	2022-05-15	criteria provided, single submitter	clinical testing	The p.G1529A variant (also known as c.4586G>C), located in coding exon 10 of the BRCA2 gene, results from a G to C substitution at nucleotide position 4586. The glycine at codon 1529 is replaced by alanine, an amino acid with similar properties. This amino acid position is conserved. 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.
University of Washington Department of Laboratory Medicine, University of Washington	RCV002342241	SCV003850635	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).
Color Diagnostics, LLC DBA Color Health	RCV002342241	SCV004362064	uncertain significance	Hereditary cancer-predisposing syndrome	2022-02-28	criteria provided, single submitter	clinical testing	This missense variant replaces glycine with alanine at codon 1529 of the BRCA2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
GeneDx	RCV004763379	SCV005372413	uncertain significance	not provided	2023-06-12	criteria provided, single submitter	clinical testing	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; Has not been previously published as pathogenic or benign to our knowledge; Also known as 4814G>C; This variant is associated with the following publications: (PMID: 9002670, 22193408, 31911673)