Submissions for variant NM_000059.4(BRCA2):c.316+12A>G

gnomAD frequency: 0.00003  dbSNP: rs186419778

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000124003	SCV000167403	benign	not specified	2014-05-15	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae	RCV000206448	SCV000260691	benign	Hereditary breast ovarian cancer syndrome	2024-01-28	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000206448	SCV000494418	benign	Hereditary breast ovarian cancer syndrome	2015-11-16	criteria provided, single submitter	clinical testing	Variant Summary: This c.316+12A>G variant in BRCA2 gene affects a non-conserved nucleotide resulting in intronic change at a position not widely known to affect normal splicing. 4/5 in silico tools via Alamut predict that this variant does not affect normal splicing. The variant of interest has been observed in control population from ExAC at an allele frequency of 24/105900 (0.02%), predominantly in Latino cohort at a frequency of 22/9822 (0.22%). This frequency in Latino cohort significantly exceeds the maximum expected allele frequency for a BRCA2 pathogenic variant (0.075%), suggesting the variant to be an ethnic-specific polymorphism. The variant of interest reportedly has been identified in an affected individual with limited information (no co-occurrence or co-segregation information provided). In an internal sample, the variant has been observed in co-occurrence with pathogenic variant, c.1236_1237dupAT in BRCA1 gene, strongly supporting for a benign outcome. Furthermore, a reputable diagnostic laboratory classifies the variant as "benign." Therefore, taken all together, this variant has been classified as benign.
Baylor Genetics	RCV000475878	SCV000541068	benign	Familial cancer of breast	2017-02-23	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000124003	SCV000602813	benign	not specified	2016-11-02	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000580994	SCV000683529	likely benign	Hereditary cancer-predisposing syndrome	2015-04-27	criteria provided, single submitter	clinical testing
Counsyl	RCV000662421	SCV000784870	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2	2017-01-18	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000679167	SCV000805686	likely benign	not provided	2017-10-24	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000124003	SCV002068185	likely benign	not specified	2017-12-19	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000124003	SCV002550244	likely benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003492564	SCV004240301	likely benign	Breast and/or ovarian cancer	2022-11-11	criteria provided, single submitter	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000679167	SCV001959092	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000124003	SCV001973203	benign	not specified		no assertion criteria provided	clinical testing