Submissions for variant NM_000059.4(BRCA2):c.6017G>C (p.Ser2006Thr)

gnomAD frequency: 0.00002  dbSNP: rs144784912

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000735579	SCV000219372	uncertain significance	Breast and/or ovarian cancer	2022-01-22	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000204206	SCV000261302	uncertain significance	Hereditary breast ovarian cancer syndrome	2023-12-02	criteria provided, single submitter	clinical testing	This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 2006 of the BRCA2 protein (p.Ser2006Thr). This variant is present in population databases (rs144784912, gnomAD 0.006%). This missense change has been observed in individual(s) with breast and/or ovarian cancer (PMID: 35918668). ClinVar contains an entry for this variant (Variation ID: 188433). 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 with a negative predictive value of 95%. 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.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000239063	SCV000296556	uncertain significance	not specified	2017-01-05	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000570534	SCV000661207	uncertain significance	Hereditary cancer-predisposing syndrome	2023-09-26	criteria provided, single submitter	clinical testing	The p.S2006T variant (also known as c.6017G>C), located in coding exon 10 of the BRCA2 gene, results from a G to C substitution at nucleotide position 6017. The serine at codon 2006 is replaced by threonine, an amino acid with similar 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.
Color Diagnostics, LLC DBA Color Health	RCV000570534	SCV000688960	uncertain significance	Hereditary cancer-predisposing syndrome	2019-03-08	criteria provided, single submitter	clinical testing
GeneDx	RCV001762394	SCV002008838	uncertain significance	not provided	2020-09-24	criteria provided, single submitter	clinical testing	Not observed at a significant frequency 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 6245G>C; This variant is associated with the following publications: (PMID: 31131967, 28726806)
University of Washington Department of Laboratory Medicine, University of Washington	RCV000570534	SCV003850861	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).
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research	RCV000735579	SCV000863717	benign	Breast and/or ovarian cancer	2014-06-02	no assertion criteria provided	clinical testing
Center for Precision Medicine, Meizhou People's Hospital	RCV002250584	SCV002520814	uncertain significance	Familial cancer of breast		no assertion criteria provided	literature only