Submissions for variant NM_000059.4(BRCA2):c.1788T>C (p.Asp596=)

gnomAD frequency: 0.00768  dbSNP: rs11571642

Total submissions: 28

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000112968	SCV000245005	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2015-01-12	reviewed by expert panel	curation	Class 1 not pathogenic based on frequency >1% in an outbred sampleset. Frequency 0.01829 (African), derived from 1000 genomes (2012-04-30).
Labcorp Genetics (formerly Invitae), Labcorp	RCV000043883	SCV000071896	benign	Hereditary breast ovarian cancer syndrome	2024-02-01	criteria provided, single submitter	clinical testing
Counsyl	RCV000112968	SCV000154065	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2014-01-09	criteria provided, single submitter	literature only
Ambry Genetics	RCV000162709	SCV000213170	benign	Hereditary cancer-predisposing syndrome	2015-11-06	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Eurofins Ntd Llc (ga)	RCV000173628	SCV000224755	benign	not specified	2014-08-06	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000397994	SCV000383637	likely benign	Fanconi anemia complementation group D1	2018-01-31	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000112968	SCV000383638	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2	2018-01-31	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000043883	SCV000494303	benign	Hereditary breast ovarian cancer syndrome	2014-04-08	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000462260	SCV000541046	benign	Familial cancer of breast	2017-02-23	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000656589	SCV000602872	benign	not provided	2023-09-21	criteria provided, single submitter	clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000162709	SCV000679709	likely benign	Hereditary cancer-predisposing syndrome	2017-07-12	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000162709	SCV000683447	benign	Hereditary cancer-predisposing syndrome	2015-04-01	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000112968	SCV000743264	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2017-07-28	criteria provided, single submitter	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000112968	SCV000744415	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2	2015-09-21	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000173628	SCV000805656	benign	not specified	2017-02-13	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000770713	SCV000902190	uncertain significance	Breast and/or ovarian cancer	2016-07-15	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000173628	SCV001470402	benign	not specified	2020-06-17	criteria provided, single submitter	clinical testing
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State	RCV000043883	SCV002026072	likely benign	Hereditary breast ovarian cancer syndrome	2022-04-19	criteria provided, single submitter	clinical testing
Genetics Program, Instituto Nacional de Cancer	RCV000043883	SCV002515250	benign	Hereditary breast ovarian cancer syndrome	2021-11-01	criteria provided, single submitter	research
Sema4, Sema4	RCV000162709	SCV002533262	benign	Hereditary cancer-predisposing syndrome	2020-03-28	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000173628	SCV002550286	benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000112968	SCV004016834	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2023-07-07	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000656589	SCV005236038	benign	not provided		criteria provided, single submitter	not provided
Breast Cancer Information Core (BIC) (BRCA2)	RCV000112968	SCV000145934	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	1997-11-13	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001353850	SCV000591766	benign	Malignant tumor of breast		no assertion criteria provided	clinical testing	The p.Asp596Asp variant has been identified in 5 individuals from our laboratory, and 13 times in the UMD-BRCA2 database. It is reported in the literature in 28 of 8092 (frequency of 0.003) probands with breast and ovarian cancers; although no control chromosomes were tested to establish the variants frequency in the general population (Borg 2010, Thomassen 2011, Caux-Moncoutier 2011, Fackenthal 2011). The p.Asp596Asp variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located near a splice junction, and is listed in dbSNP database as coming from a "clinical source" (ID#: rs11571642) with an average heterozygosity of 0.013+/-0.079 increasing the likelihood that this is a low frequency benign variant. This variant listed in one proband in our laboratory and one from the UMD database, both of which carried a second pathogenic mutation and breast or ovarian cancer phenotype, increasing the likelihood this variant does not have clinical significance. In addition, Myriad genetics has reported this variant as a polymorphism increasing the likelihood this variant is benign (personal communication). In summary, based on the above information, this variant is classified as benign.
Mayo Clinic Laboratories, Mayo Clinic	RCV000656589	SCV000778647	benign	not provided	2017-11-20	no assertion criteria provided	clinical testing
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000173628	SCV001905969	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000173628	SCV001953340	benign	not specified		no assertion criteria provided	clinical testing