Submissions for variant NM_000059.4(BRCA2):c.8866G>C (p.Glu2956Gln)

gnomAD frequency: 0.00001  dbSNP: rs142040996

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000220440	SCV000276568	uncertain significance	Hereditary cancer-predisposing syndrome	2023-04-18	criteria provided, single submitter	clinical testing	The p.E2956Q variant (also known as c.8866G>C), located in coding exon 21 of the BRCA2 gene, results from a G to C substitution at nucleotide position 8866. The glutamic acid at codon 2956 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is 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 altetration remains unclear.
GeneDx	RCV000589427	SCV000565943	uncertain significance	not provided	2022-11-23	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Also known as 9094G>C; This variant is associated with the following publications: (PMID: 12228710, 31853058, 29884841, 32377563)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589427	SCV000695181	uncertain significance	not provided	2016-03-08	criteria provided, single submitter	clinical testing	Variant summary: c.8866G>C affects a conserved nucleotide, resulting in amino acid change from Glu to Gln. 3/4 in-silico tools predict this variant to be damaging (SNPs&GO not captured due to low reliability index). This variant was not found in 120628 control chromosomes. The variant of interest has not been reported in affected individuals via publications and/or reputable databases/clinical laboratories; nor evaluated for functional impact by in vivo/vitro studies. SCRP via ClinVar lists variant as VUS. Considering all, because of the absence of clinical information and the lack of functional studies, the variant was classified as a variant of uncertain significance (VUS) until additional information becomes available.
Counsyl	RCV000031771	SCV000785615	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2017-10-17	criteria provided, single submitter	clinical testing
Invitae	RCV000690405	SCV000818089	likely benign	Hereditary breast ovarian cancer syndrome	2023-10-26	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000220440	SCV000906466	likely benign	Hereditary cancer-predisposing syndrome	2016-04-08	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000589427	SCV001133950	uncertain significance	not provided	2019-05-09	criteria provided, single submitter	clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000690405	SCV004228151	uncertain significance	Hereditary breast ovarian cancer syndrome	2023-10-10	criteria provided, single submitter	clinical testing
Sharing Clinical Reports Project (SCRP)	RCV000031771	SCV000054379	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2009-06-18	no assertion criteria provided	clinical testing