Submissions for variant NM_000059.4(BRCA2):c.6943A>C (p.Ile2315Leu)

gnomAD frequency: 0.00001  dbSNP: rs80358918

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000130766	SCV000185659	likely benign	Hereditary cancer-predisposing syndrome	2018-04-11	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
GeneDx	RCV000587113	SCV000210640	likely benign	not provided	2018-08-22	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 20104584, 10882858, 22752604, 26733283)
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000587113	SCV000600725	uncertain significance	not provided	2023-03-02	criteria provided, single submitter	clinical testing	The frequency of this variant in the general population, 0.00011 (14/128486 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported in individuals with breast cancer (PMIDs: 33471991 (2021) see also LOVD (https://databases.lovd.nl/shared/variants/BRCA2), 22752604 (2012), 21520273 (2011), 20104584 (2010), 10882858 (2000)), and healthy individuals (PMID: 33471991 (2021) see also LOVD (https://databases.lovd.nl/shared/variants/BRCA2)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000587113	SCV000695011	uncertain significance	not provided	2016-12-22	criteria provided, single submitter	clinical testing	Variant summary: The BRCA2 c.6943A>C (p.Ile2315Leu) variant involves the alteration of a not conserved nucleotide. 4/4 in silico tools predict a benign outcome for this variant (SNP&Go not captured due to low reliability index). This variant was found in 10/116052 control chromosomes at a frequency of 0.0000862, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503). This variant has been reported in multiple affected individuals without strong evidence for causality. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance. Taken together, this variant is classified as VUS.
Color Diagnostics, LLC DBA Color Health	RCV000130766	SCV000911098	likely benign	Hereditary cancer-predisposing syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Invitae	RCV001345343	SCV001539454	likely benign	Hereditary breast ovarian cancer syndrome	2024-01-24	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000130766	SCV002536285	likely benign	Hereditary cancer-predisposing syndrome	2021-10-22	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV003493423	SCV004243054	likely benign	not specified	2024-02-06	criteria provided, single submitter	clinical testing
Breast Cancer Information Core (BIC) (BRCA2)	RCV000113675	SCV000146975	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	1999-04-12	no assertion criteria provided	clinical testing
BRCAlab, Lund University	RCV000113675	SCV004243746	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2020-03-02	no assertion criteria provided	clinical testing