Submissions for variant NM_000059.4(BRCA2):c.6513G>C (p.Val2171=)

dbSNP: rs206076

Total submissions: 29

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000119246	SCV000245036	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 0.8902 (African), derived from 1000 genomes (2012-04-30).
Counsyl	RCV000119246	SCV000154059	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2014-01-02	criteria provided, single submitter	literature only	High frequency in a 1kG or ESP population: 99.9 %.
GeneDx	RCV000152878	SCV000167382	benign	not specified	2014-06-23	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.
Michigan Medical Genetics Laboratories, University of Michigan	RCV000119246	SCV000195998	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2014-11-03	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000152878	SCV000202293	benign	not specified	2018-03-06	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000162377	SCV000212687	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.
PreventionGenetics, part of Exact Sciences	RCV000152878	SCV000301767	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000261979	SCV000383746	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	RCV000119246	SCV000383747	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	RCV000257903	SCV000494339	benign	Hereditary breast ovarian cancer syndrome	2013-12-20	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000162377	SCV000537316	benign	Hereditary cancer-predisposing syndrome	2015-03-31	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000464673	SCV000541018	benign	Familial cancer of breast	2017-02-23	criteria provided, single submitter	clinical testing
Cancer Genetics and Genomics Laboratory, British Columbia Cancer Agency	RCV000152878	SCV000586969	benign	not specified	2017-04-18	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000656614	SCV000602743	benign	not provided	2023-11-30	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000152878	SCV000605771	benign	not specified	2016-12-19	criteria provided, single submitter	clinical testing	This variant is not expected to have clinical significance because it does not a lter an amino acid residue and is not located within the splice consensus sequen ce. It has been identified in over 99% of total chromosomes by the Exome Aggreg ation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs206076).
Invitae	RCV000257903	SCV000635514	benign	Hereditary breast ovarian cancer syndrome	2024-02-01	criteria provided, single submitter	clinical testing
GeneKor MSA	RCV000152878	SCV000693639	benign	not specified	2017-11-01	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000119246	SCV000743322	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2014-10-10	criteria provided, single submitter	clinical testing
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State	RCV000257903	SCV002025800	benign	Hereditary breast ovarian cancer syndrome	2022-04-19	criteria provided, single submitter	clinical testing
GreenArray Genomic Research & Solutions of Accurate Diagnostic Private Limited	RCV000119246	SCV002097618	benign	Breast-ovarian cancer, familial, susceptibility to, 2		criteria provided, single submitter	clinical testing
Genetics Program, Instituto Nacional de Cancer	RCV000257903	SCV002515135	benign	Hereditary breast ovarian cancer syndrome	2021-11-01	criteria provided, single submitter	research
Sema4, Sema4	RCV000162377	SCV002536241	benign	Hereditary cancer-predisposing syndrome	2019-12-09	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000152878	SCV002760727	benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000119246	SCV004016807	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2023-07-07	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001353926	SCV000592061	benign	Malignant tumor of breast		no assertion criteria provided	clinical testing	The p.Val2171Val variant has been identified in 8 out of 888 proband chromosomes (frequency 0.009) in individuals with breast and ovarian cancer phenotype, and also identified in 16 of 438 control chromosomes (frequency 0.037), therefore increasing the likelihood of this variant to be benign (Wagner 1999, Fackenthal 2005, Manguoglu 2001, Giannini 2006, Morgan 2010). This variant is also listed in dbSNP database as coming from a "clinical source" (ID#: rs206076) with an average heterozygosity of 0.061+/-0.164 in diverse human population, further suggesting the benign nature of this variant. This variant is not expected to have clinical significance because it does not alter an amino acid residue, and is not located near a splice junction, and in the UMD database, it has been identified in 11 (out of 48) individuals with breast or ovarian cancers, where a second pathogenic BRCA1 or BRCA2 mutation was also detected. 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
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000119246	SCV000733283	benign	Breast-ovarian cancer, familial, susceptibility to, 2		no assertion criteria provided	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000656614	SCV000778699	benign	not provided	2016-11-28	no assertion criteria provided	clinical testing
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000152878	SCV001906399	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000152878	SCV001958810	benign	not specified		no assertion criteria provided	clinical testing