Submissions for variant NM_000059.4(BRCA2):c.2229T>C (p.His743=)

gnomAD frequency: 0.03698  dbSNP: rs1801499

Total submissions: 32

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000113024	SCV000245023	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 0.1031 (Asian), 0.01423 (African), 0.03694 (European), derived from 1000 genomes (2012-04-30).
Counsyl	RCV000113024	SCV000154061	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: 3.7 %.
GeneDx	RCV000173973	SCV000167341	benign	not specified	2013-09-27	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.
Ambry Genetics	RCV000130972	SCV000185887	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	RCV000113024	SCV000195968	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2014-11-03	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000173973	SCV000225184	benign	not specified	2015-06-30	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000173973	SCV000301758	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000333511	SCV000383647	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	RCV000113024	SCV000383648	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	RCV000381055	SCV000494308	benign	Hereditary breast ovarian cancer syndrome	2014-01-13	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000130972	SCV000537349	benign	Hereditary cancer-predisposing syndrome	2015-03-31	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000462704	SCV000541029	benign	Familial cancer of breast	2017-02-23	criteria provided, single submitter	clinical testing
Cancer Genetics and Genomics Laboratory, British Columbia Cancer Agency	RCV000173973	SCV000586934	benign	not specified	2017-04-18	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000656591	SCV000602761	benign	not provided	2023-11-29	criteria provided, single submitter	clinical testing
GeneKor MSA	RCV000173973	SCV000693633	benign	not specified	2017-11-01	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000113024	SCV000743272	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2014-10-10	criteria provided, single submitter	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000113024	SCV000744425	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2015-09-21	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000755640	SCV000883037	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	2018-10-31	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000381055	SCV001000606	benign	Hereditary breast ovarian cancer syndrome	2024-02-01	criteria provided, single submitter	clinical testing
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State	RCV000381055	SCV002026074	benign	Hereditary breast ovarian cancer syndrome	2022-04-19	criteria provided, single submitter	clinical testing
GreenArray Genomic Research & Solutions of Accurate Diagnostic Private Limited	RCV000113024	SCV002097615	benign	Breast-ovarian cancer, familial, susceptibility to, 2		criteria provided, single submitter	clinical testing
Genetics Program, Instituto Nacional de Cancer	RCV000381055	SCV002515256	benign	Hereditary breast ovarian cancer syndrome	2021-11-01	criteria provided, single submitter	research
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000173973	SCV002550301	benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000113024	SCV004016820	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2023-07-07	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000656591	SCV005236044	benign	not provided		criteria provided, single submitter	not provided
Breast Cancer Information Core (BIC) (BRCA2)	RCV000113024	SCV000146018	not provided	Breast-ovarian cancer, familial, susceptibility to, 2		no assertion provided	clinical testing
Sharing Clinical Reports Project (SCRP)	RCV000113024	SCV000189298	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2011-03-15	no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000113024	SCV000733238	benign	Breast-ovarian cancer, familial, susceptibility to, 2		no assertion criteria provided	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000656591	SCV000778652	benign	not provided	2017-03-06	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000173973	SCV001552778	benign	not specified		no assertion criteria provided	clinical testing	#N/A
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000173973	SCV001906212	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000173973	SCV001956849	benign	not specified		no assertion criteria provided	clinical testing