ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.7934del (p.Arg2645fs)

dbSNP: rs80359688
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Total submissions: 16
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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) RCV000077418 SCV000282452 pathogenic Breast-ovarian cancer, familial, susceptibility to, 2 2016-04-22 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Labcorp Genetics (formerly Invitae), Labcorp RCV000257923 SCV000073361 pathogenic Hereditary breast ovarian cancer syndrome 2024-01-28 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg2645Asnfs*3) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer (PMID: 8988179, 22638694, 23885733, 24728189, 26577449, 26915939). This variant is also known as 8162delG. ClinVar contains an entry for this variant (Variation ID: 52440). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000132051 SCV000187113 pathogenic Hereditary cancer-predisposing syndrome 2023-07-12 criteria provided, single submitter clinical testing The c.7934delG pathogenic mutation, located in coding exon 16 of the BRCA2 gene, results from a deletion of one nucleotide at nucleotide position 7934, causing a translational frameshift with a predicted alternate stop codon (p.R2645Nfs*3). This pathogenic mutation has been reported in one family with three individuals affected with breast cancer at or under the age of 60 (Gayther SA et al. Nat Genet. 1997 Jan;15(1):103-5). This pathogenic mutation is also a well described African founder mutation (van der Merwe NC et al. Clin Genet. 2012 Feb;81(2):179-84; Schoeman M et al. S Afr Med J. 2013 Jun 25;103(8):529-33; Meyer S et al. J Med Genet. 2014 Feb;51(2):71-5; Seymour HJ et al. S. Afr. Med. J., 2016 Feb;106:264-7). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Of note, this may also be referred to as 8162delG in some literature. In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077418 SCV000327767 pathogenic Breast-ovarian cancer, familial, susceptibility to, 2 2015-10-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000506376 SCV000600772 pathogenic not provided 2017-06-12 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000257923 SCV000695109 pathogenic Hereditary breast ovarian cancer syndrome 2016-07-12 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.7934delG (p.Arg2645Asnfs) variant located in the helical domain (Interpro) results in a premature termination codon, predicted to cause a truncated or absent BRCA2 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant of interest was not observed in controls (ExAC, 1000 Gs or ESP) and has been reported in multiple affected individuals. The variant of interest has been indicated to be an Afrikaner founder mutation. Multiple reputable databases/clinical laboratories cite the variant as "pathogenic." Therefore, taking all available lines of evidence into consideration, the variant of interest is classified as Pathogenic.
Color Diagnostics, LLC DBA Color Health RCV000132051 SCV001356102 pathogenic Hereditary cancer-predisposing syndrome 2023-12-29 criteria provided, single submitter clinical testing This variant deletes 1 nucleotide in exon 17 of the BRCA2 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant is a well-known South African founder mutation and has been reported in more than 10 individuals affected with breast and ovarian cancer (PMID: 8988179, 22638694, 23885733, 24728189, 26577449, 26915939, 32375709, 33471991; Leiden Open Variation Database DB-ID BRCA2_001450, 34660253, Color internal data). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State RCV000257923 SCV002025834 pathogenic Hereditary breast ovarian cancer syndrome 2022-04-19 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000506376 SCV003812408 pathogenic not provided 2022-02-22 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV003149692 SCV003838835 pathogenic Breast and/or ovarian cancer 2021-10-06 criteria provided, single submitter clinical testing
Baylor Genetics RCV003473410 SCV004210496 pathogenic Familial cancer of breast 2022-09-08 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000506376 SCV005414163 pathogenic not provided 2024-04-23 criteria provided, single submitter clinical testing PM2, PM5_strong, PVS1
Sharing Clinical Reports Project (SCRP) RCV000077418 SCV000109216 pathogenic Breast-ovarian cancer, familial, susceptibility to, 2 2012-03-30 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077418 SCV000147222 pathogenic Breast-ovarian cancer, familial, susceptibility to, 2 1999-03-23 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto RCV000257923 SCV000587922 pathogenic Hereditary breast ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
GenomeConnect - Invitae Patient Insights Network RCV001535707 SCV001749791 not provided Fanconi anemia complementation group D1; Hereditary breast ovarian cancer syndrome no assertion provided phenotyping only Variant interpreted as Pathogenic and reported on 10-07-2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.

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