Submissions for variant NM_000059.4(BRCA2):c.6859A>G (p.Arg2287Gly)

dbSNP: rs876661261

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000213393	SCV000279918	uncertain significance	not provided	2016-02-22	criteria provided, single submitter	clinical testing	This variant is denoted BRCA2 c.6859A>G at the cDNA level, p.Arg2287Gly (R2287G) at the protein level, and results in the change of an Arginine to a Glycine (AGA>GGA). Using alternate nomenclature, this variant would be defined as BRCA2 7087A>G. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Arg2287Gly was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Arginine and Glycine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA2 Arg2287Gly occurs at a position that is conserved across species and is not located in a known functional domain. In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, it is unclear whether BRCA2 Arg2287Gly is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics	RCV001025736	SCV001187983	uncertain significance	Hereditary cancer-predisposing syndrome	2023-04-14	criteria provided, single submitter	clinical testing	The p.R2287G variant (also known as c.6859A>G), located in coding exon 11 of the BRCA2 gene, results from an A to G substitution at nucleotide position 6859. The arginine at codon 2287 is replaced by glycine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001220368	SCV001392354	uncertain significance	Hereditary breast ovarian cancer syndrome	2023-07-15	criteria provided, single submitter	clinical testing	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. 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: 234856). 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 arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 2287 of the BRCA2 protein (p.Arg2287Gly).