ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8940dup (p.Glu2981fs) (rs80359732)

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Total submissions: 7
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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) RCV000031778 SCV000301321 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031778 SCV000327996 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
GeneDx RCV000480621 SCV000565765 pathogenic not provided 2016-08-01 criteria provided, single submitter clinical testing This duplication of one nucleotide in BRCA2 is denoted c.8940dupA at the cDNA level and p.Glu2981ArgfsX37 (E2981RfsX37) at the protein level. The normal sequence, with the base that is duplicated in braces, is CAAAAAA[A]GAAA. The duplication causes a frameshift which changes a Glutamic Acid to an Arginine at codon 2981, and creates a premature stop codon at position 37 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.8940dupA, also reported as 9168insA, has been reported in at least one individual with early-onset breast cancer (Lee 2008). We consider this variant to be pathogenic.
Ambry Genetics RCV000563322 SCV000665364 pathogenic Hereditary cancer-predisposing syndrome 2017-05-30 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)
Invitae RCV000808015 SCV000948099 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-16 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu2981Argfs*37) 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 an individual with breast cancer (PMID: 18284688). This variant is also known as c.9168insA in the literature. ClinVar contains an entry for this variant (Variation ID: 38195). 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) RCV000031778 SCV000054386 pathogenic Breast-ovarian cancer, familial 2 2010-06-09 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031778 SCV000147490 pathogenic Breast-ovarian cancer, familial 2 2003-12-23 no assertion criteria provided clinical testing

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