Submissions for variant NM_000059.4(BRCA2):c.1362A>G (p.Lys454=)

gnomAD frequency: 0.00006  dbSNP: rs55919657

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000112912	SCV000578014	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2017-06-29	reviewed by expert panel	curation	Synonymous substitution variant, with low bioinformatic likelihood to alter mRNA splicing (splicing prior 0.02; http://priors.hci.utah.edu/PRIORS/) and frequency 0.0041 (East Asian), derived from ExAC (2014-12-17).
Labcorp Genetics (formerly Invitae), Labcorp	RCV001080149	SCV000071801	benign	Hereditary breast ovarian cancer syndrome	2024-02-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000162634	SCV000213070	likely benign	Hereditary cancer-predisposing syndrome	2014-10-29	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.
PreventionGenetics, part of Exact Sciences	RCV000252883	SCV000301754	benign	not specified		criteria provided, single submitter	clinical testing
Counsyl	RCV000112912	SCV000488181	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2	2016-02-19	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000461568	SCV000541069	benign	Familial cancer of breast	2017-02-23	criteria provided, single submitter	clinical testing
Cancer Genetics and Genomics Laboratory, British Columbia Cancer Agency	RCV000252883	SCV000586926	benign	not specified	2017-04-18	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000252883	SCV000593702	likely benign	not specified	2015-10-07	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000162634	SCV000683417	likely benign	Hereditary cancer-predisposing syndrome	2015-04-22	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000755877	SCV000883520	benign	not provided	2018-04-24	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000162634	SCV002533228	benign	Hereditary cancer-predisposing syndrome	2020-10-29	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000252883	SCV004242793	benign	not specified	2024-02-06	criteria provided, single submitter	clinical testing
Breast Cancer Information Core (BIC) (BRCA2)	RCV000112912	SCV000145858	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2010-09-18	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000252883	SCV000591738	benign	not specified		no assertion criteria provided	clinical testing	This variant is not expected to have clinical significance because it occurs at a poorly conserved residue, does not alter an amino acid residue, is not located near a splice junction, is listed in dbSNP (rs55919657) and the 1000 genome project, and is reported as not clinically important in the BIC database. Based on the above information this variant is classified as benign.