Submissions for variant NM_000059.4(BRCA2):c.7907G>A (p.Cys2636Tyr)

dbSNP: rs2137577318

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002032666	SCV002190568	uncertain significance	Hereditary breast ovarian cancer syndrome	2021-09-23	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. This sequence change replaces cysteine with tyrosine at codon 2636 of the BRCA2 protein (p.Cys2636Tyr). The cysteine residue is weakly conserved and there is a large physicochemical difference between cysteine and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. 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.
Ambry Genetics	RCV004946727	SCV005548569	uncertain significance	Hereditary cancer-predisposing syndrome	2024-10-25	criteria provided, single submitter	clinical testing	The p.C2636Y variant (also known as c.7907G>A), located in coding exon 16 of the BRCA2 gene, results from a G to A substitution at nucleotide position 7907. The cysteine at codon 2636 is replaced by tyrosine, an amino acid with highly dissimilar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV001694176	SCV001906125	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001694176	SCV001964908	likely benign	not provided		no assertion criteria provided	clinical testing