ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.6347A>G (p.His2116Arg) (rs55953736)

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Total submissions: 29
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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) RCV000113577 SCV000321286 benign Breast-ovarian cancer, familial 2 2016-09-28 reviewed by expert panel curation Class 1 not pathogenic based on frequency >1% in an outbred sampleset. Frequency 0.025 (African), derived from 1000 genomes (2013-05-02).
Invitae RCV000167845 SCV000072932 benign Hereditary breast and ovarian cancer syndrome 2020-12-07 criteria provided, single submitter clinical testing
Counsyl RCV000113577 SCV000154071 likely benign Breast-ovarian cancer, familial 2 2014-02-18 criteria provided, single submitter literature only
Ambry Genetics RCV000131142 SCV000186080 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.
Michigan Medical Genetics Laboratories,University of Michigan RCV000113577 SCV000195997 benign Breast-ovarian cancer, familial 2 2014-11-03 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000120324 SCV000225190 benign not specified 2015-07-08 criteria provided, single submitter clinical testing
Vantari Genetics RCV000131142 SCV000267021 likely benign Hereditary cancer-predisposing syndrome 2016-01-04 criteria provided, single submitter clinical testing
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia RCV000167845 SCV000296856 benign Hereditary breast and ovarian cancer syndrome 2015-10-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000113577 SCV000383742 likely benign Breast-ovarian cancer, familial 2 2018-06-20 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 RCV000395640 SCV000383743 likely benign Fanconi anemia, complementation group D1 2018-06-20 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000167845 SCV000494337 benign Hereditary breast and ovarian cancer syndrome 2014-03-12 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000034456 SCV000511251 likely benign not provided 2016-09-20 criteria provided, single submitter clinical testing Converted during submission to Likely benign.
Fulgent Genetics,Fulgent Genetics RCV000113577 SCV000575757 likely benign Breast-ovarian cancer, familial 2 2015-11-24 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000120324 SCV000593723 benign not specified 2017-10-25 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001283021 SCV000602846 benign none provided 2020-09-01 criteria provided, single submitter clinical testing
Color Health, Inc RCV000131142 SCV000683776 benign Hereditary cancer-predisposing syndrome 2015-03-11 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000113577 SCV000743320 likely benign Breast-ovarian cancer, familial 2 2015-06-15 criteria provided, single submitter clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000113577 SCV000744488 benign Breast-ovarian cancer, familial 2 2017-05-31 criteria provided, single submitter clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C. RCV000131142 SCV000747814 likely benign Hereditary cancer-predisposing syndrome 2018-01-16 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000120324 SCV000805742 benign not specified 2016-12-12 criteria provided, single submitter clinical testing
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034456 SCV000043223 probably not pathogenic not provided 2012-07-13 no assertion criteria provided research Converted during submission to Likely benign.
ITMI RCV000120324 SCV000084476 not provided not specified 2013-09-19 no assertion provided reference population
Breast Cancer Information Core (BIC) (BRCA2) RCV000113577 SCV000146832 benign Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
CSER _CC_NCGL, University of Washington RCV000148423 SCV000190122 likely benign Breast and/or ovarian cancer 2014-06-01 no assertion criteria provided research
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000120324 SCV000592045 benign not specified no assertion criteria provided clinical testing The p.His2116Arg variant has been reported in the literature in 13/19710 proband chromosomes of individuals with breast cancer and prostate cancer; it was not detected in the 122 control chromosomes tested (Berg_2012_22995991, Borg_2010_20104584, Carvalho_2007_17308087, Caux-Moncoutier_2011_21120943, Haffty_2006_15983021, Johnston_2012_22703879, Kote-Jarai_2011_21952622, Lee_2008_18284688, Tazzite_2012_22425665), however, an insufficient number of controls were included in these studies to determine the frequency of this variant in the general population. It has also been reported in the HGMD, BIC(x88 as not clinically important), Exome Variant Server and BOCs databases. It is listed in dbSNP database as coming from a "clinical source" (ID#: rs55953736) with a global minor allele frequency (MAF) of 0.002 (1000 Genomes) and was also identified by the EVS project as a low frequency variant. This residue is not conserved in mammals and computational analyses (PolyPhen, SIFT, AlignGVGD) provide inconsistent predictions regarding the impact to the protein and this information is not very predictive of pathogenicity. It was identified 18x in the UMD database, 6x as co-occuring with a second pathogenic variant, increasing the likelihood this variant does not have clinical significance. Furthermore, Myriad genetics classifies this variant as a polymorphism (personal communication). In summary, this variant meets our criteria to be classified as benign.
True Health Diagnostics RCV000131142 SCV000787940 likely benign Hereditary cancer-predisposing syndrome 2018-01-24 no assertion criteria provided clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000034456 SCV001800811 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics Laboratory, Department of Pathology,Netherlands Cancer Institute RCV000120324 SCV001906353 benign not specified no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000120324 SCV001955584 benign not specified no assertion criteria provided clinical testing

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