Submissions for variant NM_000059.4(BRCA2):c.7418G>T (p.Cys2473Phe)

dbSNP: rs55924966

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001776482	SCV002013088	uncertain significance	not provided	2021-02-09	criteria provided, single submitter	clinical testing	Not observed in large population cohorts (Lek 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 7646G>T
Ambry Genetics	RCV002386554	SCV002668374	uncertain significance	Hereditary cancer-predisposing syndrome	2024-03-18	criteria provided, single submitter	clinical testing	The p.C2473F variant (also known as c.7418G>T), located in coding exon 13 of the BRCA2 gene, results from a G to T substitution at nucleotide position 7418. The cysteine at codon 2473 is replaced by phenylalanine, an amino acid with highly 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002541062	SCV003207980	uncertain significance	Hereditary breast ovarian cancer syndrome	2022-06-14	criteria provided, single submitter	clinical testing	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. ClinVar contains an entry for this variant (Variation ID: 1320503). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with phenylalanine, which is neutral and non-polar, at codon 2473 of the BRCA2 protein (p.Cys2473Phe). 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003388044	SCV004100265	uncertain significance	not specified	2023-09-29	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV001776482	SCV004220553	uncertain significance	not provided	2023-08-30	criteria provided, single submitter	clinical testing	This variant has not been reported in any individuals affected with BRCA2 related disease in the published literature. It also has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.