ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8673_8674del (p.Arg2892fs) (rs80359724)

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Total submissions: 10
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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) RCV000113985 SCV000301301 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Invitae RCV000045598 SCV000073611 pathogenic Hereditary breast and ovarian cancer syndrome 2018-11-12 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg2892Thrfs*14) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA2-related disease. ClinVar contains an entry for this variant (Variation ID: 52656). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000222868 SCV000279351 pathogenic not provided 2015-05-22 criteria provided, single submitter clinical testing This deletion of 2 nucleotides in BRCA2 is denoted c.8673_8674delAA at the cDNA level and p.Arg2892ThrfsX14 (R2892TfsX14) at the protein level. Using alternate nomenclature, this variant would be defined as BRCA2 8901delAA. The normal sequence, with the bases that are deleted in braces, is TAAC[AA]GACA. The deletion causes a frameshift, which changes an Arginine to a Threonine at codon 2892, and creates a premature stop codon at position 14 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. We consider this variant to be pathogenic.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000113985 SCV000327945 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000045598 SCV000592219 pathogenic Hereditary breast and ovarian cancer syndrome criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000222868 SCV000600819 pathogenic not provided 2015-11-24 criteria provided, single submitter clinical testing
Ambry Genetics RCV000509975 SCV000608128 pathogenic Hereditary cancer-predisposing syndrome 2017-01-26 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000222868 SCV000883498 pathogenic not provided 2018-01-18 criteria provided, single submitter clinical testing The BRCA2 c.8673_8674delAA; p.Arg2892fs variant (rs80359724), is not reported in the medical literature but is reported as pathogenic by multiple laboratories in ClinVar (Variation ID: 52656). This variant is also absent from the general population databases (1000 Genomes Project, Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. This variant deletes two nucleotides causing a frameshift, and is predicted to result in a truncated protein or absent transcript. Based on the above information, this variant is considered pathogenic.
Breast Cancer Information Core (BIC) (BRCA2) RCV000113985 SCV000147436 pathogenic Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000045598 SCV000587967 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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