ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8340_8343del (p.Asn2781fs) (rs80359707)

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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) RCV000077434 SCV000301265 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Ambry Genetics RCV000162939 SCV000213426 pathogenic Hereditary cancer-predisposing syndrome 2016-05-06 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)
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077434 SCV000327875 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000077434 SCV000487967 pathogenic Breast-ovarian cancer, familial 2 2015-12-13 criteria provided, single submitter clinical testing
GeneDx RCV000480653 SCV000568493 pathogenic not provided 2016-03-22 criteria provided, single submitter clinical testing This deletion of 4 nucleotides in BRCA2 is denoted c.8340_8343delTAAC at the cDNA level and p.Asn2781ValfsX39 (N2781VfsX39) at the protein level. Using alternate nomenclature, this variant has been published as BRCA2 8568del4. The normal sequence, with the bases that are deleted in braces, is CTGC[TAAC]AGTA. The deletion causes a frameshift which changes an Asparagine to a Valine at codon 2781, and creates a premature stop codon at position 39 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA2 c.8340_8343delTAAC has been observed in individuals with breast and/or ovarian cancer (Risch 2006, Litton 2012). We consider this variant to be pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000480653 SCV000600795 pathogenic not provided 2016-11-17 criteria provided, single submitter clinical testing
Invitae RCV000496829 SCV000942527 pathogenic Hereditary breast and ovarian cancer syndrome 2019-01-01 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asn2781Valfs*39) 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 been reported in the literature in individuals affected with breast and/or ovarian cancer (PMID: 17148771, 21324516, 21913181). This variant is also known as 8568delTAAC or 8568del4 in the literature. ClinVar contains an entry for this variant (Variation ID: 52556). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Sharing Clinical Reports Project (SCRP) RCV000077434 SCV000109232 pathogenic Breast-ovarian cancer, familial 2 2007-10-18 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077434 SCV000147327 pathogenic Breast-ovarian cancer, familial 2 2003-12-23 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000496829 SCV000587949 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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