ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8394_8396delinsAA (p.Arg2799fs) (rs276174907)

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Total submissions: 6
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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) RCV000113924 SCV000301274 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000497283 SCV000210794 pathogenic not provided 2014-01-14 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA2 c.8394_8396delTAGinsAA at the cDNA level and p.Arg2799AsnfsX22 (R2799NfsX22) at the protein level. The normal sequence, with the bases that are deleted and inserted in brackets, is ACCC[delTAG][insAA]ACCT. The deletion and insertion cause a frameshift, which changes an Arginine to an Asparagine at codon 2799, and creates a premature stop codon at position 22 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.8394_8396delTAGinsAA, previously reported as 8622delTAGinsAA using alternative nomenclature, has been reported in association with hereditary breast and/or ovarian cancer (Schrader 2012) and is listed as clinically important in the Breast Cancer Information Core (BIC) database.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000113924 SCV000327886 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Invitae RCV000496383 SCV000947115 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-10 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg2799Asnfs*22) 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 observed in several individuals affected with breast, pancreatic and ovarian cancer (PMID: 22776961, 26681312). This variant is also known as 8622delTAGinsAA and c.8394_8396delTAGinsAA in the literature. ClinVar contains an entry for this variant (Variation ID: 52573). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Breast Cancer Information Core (BIC) (BRCA2) RCV000113924 SCV000147353 pathogenic Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000496383 SCV000587953 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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