Submissions for variant NM_000059.4(BRCA2):c.8551G>T (p.Ala2851Ser)

gnomAD frequency: 0.00001  dbSNP: rs876658592

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000223606	SCV000274047	uncertain significance	Hereditary cancer-predisposing syndrome	2022-12-10	criteria provided, single submitter	clinical testing	The p.A2851S variant (also known as c.8551G>T and 8779G>T), located in coding exon 19 of the BRCA2 gene, results from a G to T substitution at nucleotide position 8551. The alanine at codon 2851 is replaced by serine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000697939	SCV000826573	uncertain significance	Hereditary breast ovarian cancer syndrome	2023-07-15	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 2851 of the BRCA2 protein (p.Ala2851Ser). This variant is present in population databases (no rsID available, gnomAD 0.01%). 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: 230484). 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. 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	RCV000223606	SCV000904891	uncertain significance	Hereditary cancer-predisposing syndrome	2019-05-04	criteria provided, single submitter	clinical testing
GeneDx	RCV001775680	SCV002013948	uncertain significance	not provided	2019-09-18	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Also known as BRCA2 c.8779G>T
Baylor Genetics	RCV003462437	SCV004213589	uncertain significance	Familial cancer of breast	2023-09-11	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV001775680	SCV004220615	uncertain significance	not provided	2023-07-14	criteria provided, single submitter	clinical testing	This variant has not been reported in individuals with BRCA2-related conditions in the published literature. The frequency of this variant in the general population, 0.000032 (1/31404 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is benign or damaging. Based on the available information, we are unable to determine the clinical significance of this variant.