Submissions for variant NM_000059.4(BRCA2):c.8460A>C (p.Val2820=)

gnomAD frequency: 0.01220  dbSNP: rs9590940

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)	RCV000113937	SCV000245176	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 0.04675 (African), derived from 1000 genomes (2012-04-30).
Invitae	RCV000045525	SCV000073538	benign	Hereditary breast ovarian cancer syndrome	2024-02-01	criteria provided, single submitter	clinical testing
Counsyl	RCV000113937	SCV000154064	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2014-01-09	criteria provided, single submitter	literature only
Ambry Genetics	RCV000128993	SCV000172887	benign	Hereditary cancer-predisposing syndrome	2014-11-19	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.
Michigan Medical Genetics Laboratories, University of Michigan	RCV000113937	SCV000196013	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2014-11-03	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000152884	SCV000202303	benign	not specified	2015-02-09	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000404467	SCV000383783	benign	Fanconi anemia complementation group D1	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV000113937	SCV000383784	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000045525	SCV000494344	benign	Hereditary breast ovarian cancer syndrome	2014-01-30	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000470439	SCV000541033	benign	Familial cancer of breast	2017-02-23	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002477152	SCV000575736	benign	Familial cancer of breast; Breast-ovarian cancer, familial, susceptibility to, 2; Fanconi anemia complementation group D1; Medulloblastoma; Wilms tumor 1; Malignant tumor of prostate; Pancreatic cancer, susceptibility to, 2; Glioma susceptibility 3	2021-12-22	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001711222	SCV000602770	benign	not provided	2023-11-22	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000128993	SCV000683967	benign	Hereditary cancer-predisposing syndrome	2015-04-13	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000152884	SCV000805780	benign	not specified	2016-11-03	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000152884	SCV001470246	benign	not specified	2020-06-16	criteria provided, single submitter	clinical testing
GeneDx	RCV001711222	SCV001939394	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State	RCV000045525	SCV002025850	benign	Hereditary breast ovarian cancer syndrome	2022-04-19	criteria provided, single submitter	clinical testing
Genetics Program, Instituto Nacional de Cancer	RCV000045525	SCV002515152	benign	Hereditary breast ovarian cancer syndrome	2021-11-01	criteria provided, single submitter	research
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000113937	SCV004016867	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2023-07-07	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000152884	SCV004027479	benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
Breast Cancer Information Core (BIC) (BRCA2)	RCV000113937	SCV000147369	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2007-01-18	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000152884	SCV000592193	benign	not specified		no assertion criteria provided	clinical testing	The p.Val2820Val variant is not expected to have clinical significance because it does not result in a change of amino acid, is not located near a splice site, is not well conserved and is recorded as a common polymorphism in public databases. dbSNPID: rs9590940. In particular it is observed at a frequency as high as 4% in A.A population from the EPS server. Myriad reports this variant as a polymorphism (personal communication) and the UMD database recorded this variant 37x and it co-occurred with a second pathogenic variant in either BRCA1 or 2 seven times. In summary, this variant is classified as benign.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000152884	SCV001799616	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000152884	SCV001906024	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000152884	SCV001929633	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000152884	SCV001952124	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000152884	SCV001969768	benign	not specified		no assertion criteria provided	clinical testing
BRCAlab, Lund University	RCV000113937	SCV004243821	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2020-03-02	no assertion criteria provided	clinical testing