Submissions for variant NM_000059.4(BRCA2):c.4367A>C (p.Glu1456Ala)

dbSNP: rs878853584

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000231677	SCV000283238	uncertain significance	Hereditary breast ovarian cancer syndrome	2016-01-29	criteria provided, single submitter	clinical testing	This sequence change replaces glutamic acid with alanine at codon 1456 of the BRCA2 protein (p.Glu1456Ala). The glutamic acid residue is moderately conserved and there is a moderate physicochemical difference between glutamic acid and alanine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a BRCA2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.
Color Diagnostics, LLC DBA Color Health	RCV001180477	SCV001345414	uncertain significance	Hereditary cancer-predisposing syndrome	2019-01-29	criteria provided, single submitter	clinical testing
University of Washington Department of Laboratory Medicine, University of Washington	RCV001180477	SCV003850455	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).