ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.6100C>T (p.Arg2034Cys) (rs1799954)

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Total submissions: 38
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000113532 SCV000244462 benign Breast-ovarian cancer, familial 2 2015-08-10 reviewed by expert panel curation IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 0.00000571
Invitae RCV000044844 SCV000072857 benign Hereditary breast and ovarian cancer syndrome 2020-11-17 criteria provided, single submitter clinical testing
Counsyl RCV000113532 SCV000154068 benign Breast-ovarian cancer, familial 2 2014-02-06 criteria provided, single submitter literature only
GeneDx RCV000120331 SCV000167377 benign not specified 2013-10-09 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 RCV000113532 SCV000195996 benign Breast-ovarian cancer, familial 2 2014-11-03 criteria provided, single submitter clinical testing
Ambry Genetics RCV000162509 SCV000212900 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: 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.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000120331 SCV000225165 benign not specified 2014-08-18 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000113532 SCV000383731 likely benign Breast-ovarian cancer, familial 2 2018-02-27 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 RCV000044844 SCV000494335 benign Hereditary breast and ovarian cancer syndrome 2014-02-14 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000034452 SCV000511453 benign not provided 2016-06-27 criteria provided, single submitter clinical testing
Baylor Genetics RCV000461415 SCV000541060 benign Familial cancer of breast 2017-02-23 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000113532 SCV000575742 likely benign Breast-ovarian cancer, familial 2 2015-11-09 criteria provided, single submitter clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C. RCV000044844 SCV000576435 likely benign Hereditary breast and ovarian cancer syndrome 2017-02-14 criteria provided, single submitter clinical testing
Cancer Genetics and Genomics Laboratory,British Columbia Cancer Agency RCV000120331 SCV000586965 benign not specified 2017-04-18 criteria provided, single submitter clinical testing
Department of Pathology and Molecular Medicine,Queen's University RCV000120331 SCV000588107 benign not specified 2017-04-20 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000120331 SCV000593721 benign not specified 2017-03-16 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001282707 SCV000602767 benign none provided 2020-08-15 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000034452 SCV000608682 likely benign not provided 2020-03-01 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000113532 SCV000743316 benign Breast-ovarian cancer, familial 2 2014-10-09 criteria provided, single submitter clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000113532 SCV000744482 benign Breast-ovarian cancer, familial 2 2015-09-21 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000120331 SCV000805734 benign not specified 2016-09-27 criteria provided, single submitter clinical testing
Color Health, Inc RCV000162509 SCV000910521 benign Hereditary cancer-predisposing syndrome 2015-10-13 criteria provided, single submitter clinical testing
Mendelics RCV000113532 SCV001139136 likely benign Breast-ovarian cancer, familial 2 2019-05-28 criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Leipzig Medical Center RCV000113532 SCV001429037 uncertain significance Breast-ovarian cancer, familial 2 2018-11-12 criteria provided, single submitter clinical testing
Research and Development, ARUP Laboratories RCV001642545 SCV001854866 benign Breast-ovarian cancer, familial 2; Breast-ovarian cancer, familial 1; Hereditary breast and ovarian cancer syndrome 2020-01-20 criteria provided, single submitter curation
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034452 SCV000043219 no known pathogenicity not provided 2012-07-13 no assertion criteria provided research Converted during submission to Benign.
ITMI RCV000120331 SCV000084483 not provided not specified 2013-09-19 no assertion provided reference population
Breast Cancer Information Core (BIC) (BRCA2) RCV000113532 SCV000146768 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Sharing Clinical Reports Project (SCRP) RCV000113532 SCV000189312 benign Breast-ovarian cancer, familial 2 2011-03-10 no assertion criteria provided clinical testing
Pathway Genomics RCV000113532 SCV000189907 likely benign Breast-ovarian cancer, familial 2 2014-07-24 no assertion criteria provided clinical testing
Department of Medical Genetics, University Hospital of North Norway RCV000113532 SCV000301450 likely benign Breast-ovarian cancer, familial 2 2016-05-01 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000120331 SCV000592030 benign not specified no assertion criteria provided clinical testing The p.Arg2034Cys variant has been identified in 42 out of 7668 proband chromosomes (frequency 0.005) in individuals with unilateral and contralateral breast cancer and familial breast and ovarian cancer phenotype, and also found in 39 out of 3186 control chromosomes (frequency 0.012) included in these studies (Johnson 2007, Schoumacher 2001, Wagner 1999, Capanu 2011, Borg 2010, Hondow 2011, Salazar 2006, Diez 2003, Simard 2006, Miramar 2008, Beristain 2007). It is also listed in dbSNP database coming from a “clinical source” (ID#: rs1799954) with a “global minor allele frequency of 0.001 (1000 genomes), therefore increasing the likelihood that this variant is benign. The p.Arg2034 is not conserved in mammals but was conserved in birds, reptiles, frogs and fish, therefore decreasing the likelihood that this variant has functional significance. Furthermore, the computational analyses (PolyPhen, SIFT, AlignGVGD) provide inconsistent predictions regarding the impact to the protein and this information is not very predictive of pathogenicity. In the UMD database, this variant has been identified in 22 (out of 137) individuals with breast or ovarian cancers, where a second pathogenic BRCA1 or BRCA2 mutation was also detected, further suggesting that this is a benign variant. In summary, based on the above information, this variant is classified as benign.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000113532 SCV000733278 benign Breast-ovarian cancer, familial 2 no assertion criteria provided clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000034452 SCV000778695 likely benign not provided 2017-02-21 no assertion criteria provided clinical testing
True Health Diagnostics RCV000162509 SCV000788118 likely benign Hereditary cancer-predisposing syndrome 2017-11-10 no assertion criteria provided clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000120331 SCV001799136 benign not specified no assertion criteria provided clinical testing
Clinical Genetics Laboratory, Department of Pathology,Netherlands Cancer Institute RCV000120331 SCV001906369 benign not specified no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000120331 SCV001955578 benign not specified no assertion criteria provided clinical testing

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