ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.1786G>C (p.Asp596His) (rs56328701)

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Total submissions: 32
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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) RCV000083088 SCV001161606 benign Breast-ovarian cancer, familial 2 2019-06-18 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 = 0.000066
Invitae RCV000043882 SCV000071895 benign Hereditary breast and ovarian cancer syndrome 2020-12-03 criteria provided, single submitter clinical testing
Counsyl RCV000083088 SCV000154038 likely benign Breast-ovarian cancer, familial 2 2014-01-02 criteria provided, single submitter literature only
Ambry Genetics RCV000131138 SCV000186074 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 RCV000083088 SCV000195962 benign Breast-ovarian cancer, familial 2 2014-11-03 criteria provided, single submitter clinical testing
GeneDx RCV000514736 SCV000210568 likely benign not provided 2021-03-01 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 17997147, 24728327, 32426482, 21952622, 21520273, 25637381, 23231788, 17513806, 27153395, 26306726, 28678401, 26517685, 28439188, 20104584, 18284688, 16284991, 31131967)
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000768622 SCV000219305 benign Breast and/or ovarian cancer 2016-03-03 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000120309 SCV000224768 likely benign not specified 2015-04-23 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000292009 SCV000383635 likely benign Fanconi anemia, complementation group D1 2018-08-30 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 RCV000083088 SCV000383636 likely benign Breast-ovarian cancer, familial 2 2018-08-30 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 RCV000120309 SCV000538484 uncertain significance not specified 2016-03-28 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: ExAC: 0.1% (45/65250) European; ClinVar: 5 LB, 3 B
Cancer Genetics and Genomics Laboratory,British Columbia Cancer Agency RCV000120309 SCV000586930 benign not specified 2017-04-18 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000514736 SCV000610856 likely benign not provided 2017-02-17 criteria provided, single submitter clinical testing
Color Health, Inc RCV000131138 SCV000683446 likely benign Hereditary cancer-predisposing syndrome 2015-02-06 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000083088 SCV000743263 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 RCV000083088 SCV000744414 benign Breast-ovarian cancer, familial 2 2015-09-21 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000120309 SCV000805655 benign not specified 2017-07-31 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001283414 SCV000885088 likely benign none provided 2020-07-06 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000514736 SCV000892063 likely benign not provided 2021-04-01 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000514736 SCV001133693 likely benign not provided 2019-01-17 criteria provided, single submitter clinical testing
Mendelics RCV000083088 SCV001139009 benign Breast-ovarian cancer, familial 2 2019-05-28 criteria provided, single submitter clinical testing
Research and Development, ARUP Laboratories RCV001642659 SCV001854690 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
ITMI RCV000120309 SCV000084461 not provided not specified 2013-09-19 no assertion provided reference population
Sharing Clinical Reports Project (SCRP) RCV000083088 SCV000115162 benign Breast-ovarian cancer, familial 2 2012-05-01 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000083088 SCV000145933 not provided Breast-ovarian cancer, familial 2 no assertion provided clinical testing
CSER _CC_NCGL, University of Washington RCV000148417 SCV000190116 likely benign Breast neoplasm 2014-06-01 no assertion criteria provided research
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001353780 SCV000591765 benign Malignant tumor of breast no assertion criteria provided clinical testing The BRCA2 p.Asp596His variant was identified in 7 of 7970 proband chromosomes (frequency: 0.001) from individuals or families with ovarian and breast cancer (Borg 2010, Brozek 2007, Lee 2008, Machado 2007, Pal 2005); however, an insufficient number of controls were included in these studies to determine the frequency of this variant in the general population. The variant was also identified by our laboratory in 2 individuals with breast cancer. The variant was identified by the Exome Variant Server project in 5 of 12995 European American/African American alleles (frequency: 0.0004), although this low number of observations and low frequency is not substantive enough to determine the prevalence of the variant in the general population and its relationship to disease. The p.Asp596 residue is conserved across most mammals, but not across lower organisms. Computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. An in silico analysis study by Lee (2008) classified this variant as low-frequency unclassified variant with medium to high risk in selected computational predictive programs; however, a population study by Pal (2005) noted that a tumour with the variant had low malignant potential. This variant was identified in dbSNP (ID: rs56328701) “With untested allele”, HGMD, ClinVar database, the BIC database (50X with no clinical importance), and UMD (44X as a neutral variant). In UMD the c.1786G>C variant was identified with five different co-occurring pathogenic BRCA1 and BRCA2 variants, increasing the likelihood that the p.Asp596His variant does not have clinical significance. In addition, the variant was classified as a benign by the Sharing Clinical Reports Project (SCRP) (submitted within the ClinVar database and derived from Myriad reports). In summary, based on the above information, this variant meets our laboratory's criteria to be classified as benign.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000083088 SCV000733233 benign Breast-ovarian cancer, familial 2 no assertion criteria provided clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000514736 SCV000778646 benign not provided 2017-04-20 no assertion criteria provided clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000120309 SCV001800392 benign not specified no assertion criteria provided clinical testing
Clinical Genetics Laboratory, Department of Pathology,Netherlands Cancer Institute RCV000120309 SCV001906061 benign not specified no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000120309 SCV001957883 benign not specified no assertion criteria provided clinical testing

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