ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.6323G>A (p.Arg2108His) (rs35029074)

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Total submissions: 30
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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) RCV000031619 SCV000244465 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 = 0.000000000000372
Invitae RCV000044912 SCV000072925 benign Hereditary breast and ovarian cancer syndrome 2020-12-07 criteria provided, single submitter clinical testing
Counsyl RCV000031619 SCV000154045 likely benign Breast-ovarian cancer, familial 2 2014-01-02 criteria provided, single submitter literature only
GeneDx RCV000168589 SCV000167379 benign not specified 2013-12-23 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.
CSER _CC_NCGL, University of Washington RCV000148434 SCV000190133 likely benign Breast neoplasm 2014-06-01 criteria provided, single submitter research
Ambry Genetics RCV000162540 SCV000212942 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.
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000768601 SCV000219377 benign Breast and/or ovarian cancer 2016-01-05 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000168589 SCV000225177 benign not specified 2014-12-11 criteria provided, single submitter clinical testing
Michigan Medical Genetics Laboratories,University of Michigan RCV000031619 SCV000267794 benign Breast-ovarian cancer, familial 2 2016-04-21 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000290378 SCV000383738 likely benign Fanconi anemia, complementation group D1 2018-03-08 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 Clinical Services Laboratory,Illumina RCV000031619 SCV000383739 likely benign Breast-ovarian cancer, familial 2 2018-03-08 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.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000168589 SCV000538467 benign not specified 2016-05-11 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: ClinVar: Ben by expert panel
Cancer Genetics and Genomics Laboratory,British Columbia Cancer Agency RCV000168589 SCV000586967 benign not specified 2017-04-18 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000168589 SCV000593722 benign not specified 2018-08-07 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000168589 SCV000602844 benign not specified 2019-03-05 criteria provided, single submitter clinical testing
Color Health, Inc RCV000162540 SCV000683774 benign Hereditary cancer-predisposing syndrome 2015-03-09 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000031619 SCV000743319 likely benign Breast-ovarian cancer, familial 2 2017-07-28 criteria provided, single submitter clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000031619 SCV000744487 benign Breast-ovarian cancer, familial 2 2015-09-21 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000656612 SCV000805740 uncertain significance not provided 2015-09-14 criteria provided, single submitter clinical testing
Mendelics RCV000031619 SCV001139145 likely benign Breast-ovarian cancer, familial 2 2019-05-28 criteria provided, single submitter clinical testing
Research and Development, ARUP Laboratories RCV001642413 SCV001854879 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
Sharing Clinical Reports Project (SCRP) RCV000031619 SCV000054226 benign Breast-ovarian cancer, familial 2 2012-10-10 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031619 SCV000146825 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Pathway Genomics RCV000031619 SCV000189896 benign Breast-ovarian cancer, familial 2 2014-07-24 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000168589 SCV000592043 benign not specified no assertion criteria provided clinical testing The p.Arg2108His variant has been reported in the literature in 14/19788 proband chromosomes in individuals with breast cancer, prostate cancer and cutaneous melanoma (Borg_2010, Caux-Moncoutier_2009, Caux-Moncoutier_2011,de Sanjose_2003, Diez_2003, Gomez-Garcia_2005, Kote-Jarai_2011, Lindor_2012, Monnerat_2007). It was not, however, found in any of the 100 control chromosomes tested. It is listed in the dbSNP database as coming from a "clinical source" (ID#:rs35029074) with a global minor allele frequency (MAF) of 0.001 (1000 Genomes), increasing the likelihood that this is a low frequency benign variant. The variant was also identified in the LOVD (X2), UMD (X68), Exome server, BIC (X127) and BOCs databases; in the latter database it was classified as a benign variant with an ACMG 5 designation. In the UMD database, this variant has been identified in nine individuals with a second pathogenic in BRCA1 [c.6078dup (p.Arg2027LysfsX22), c.1440_1441delCA (p.Ile481SerfsX32)] and BRCA2 [c.IVS16+6T>C (c.4986+6T>C), c.442_4357del (p.Glu149TyrfsX2), c.4485_4675del (p.Ser1496GlyfsX14), c.2679_2682delGAAA (p.Lys893AsnfsX106)], thereby increasing the likelihood that this variant does not have clinical significance. This residue is not conserved in mammals and the variant amino acid Histidine (His) is present in chicken at this position, increasing the likelihood that an alteration to this residue may not have functional significance. Computational analyses (PolyPhen, SIFT, AlignGVGD) do not predict any effect on the protein function, however, this information is not predictive enough to assume pathogenicity. In summary, based on the above information, this variant is classified as benign.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000031619 SCV000733280 benign Breast-ovarian cancer, familial 2 no assertion criteria provided clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000656612 SCV000778697 benign not provided 2017-02-20 no assertion criteria provided clinical testing
True Health Diagnostics RCV000162540 SCV000787939 likely benign Hereditary cancer-predisposing syndrome 2017-12-08 no assertion criteria provided clinical testing
Clinical Genetics Laboratory, Department of Pathology,Netherlands Cancer Institute RCV000168589 SCV001906336 benign not specified no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000168589 SCV001951816 benign not specified no assertion criteria provided clinical testing

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