ClinVar Miner

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

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Total submissions: 3
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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) RCV000661598 SCV000783895 pathogenic Breast-ovarian cancer, familial 2 2017-12-15 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000485298 SCV000565775 pathogenic not provided 2018-11-02 criteria provided, single submitter clinical testing This deletion of one nucleotide in BRCA2 is denoted c.8940delA at the cDNA level and p.Glu2981LysfsX7 (E2981KfsX7) at the protein level. The normal sequence, with the base that is deleted in braces, is CAAAAAA[A]GAAA. The deletion causes a frameshift which changes a Glutamic Acid to a Lysine at codon 2981, and creates a premature stop codon at position 7 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.8940delA, also defined as c.8934delA or 9168delA by alternate nomenclature, has been reported in at least one patient with breast cancer (Lin 2016). We consider this variant to be pathogenic.
Invitae RCV000688113 SCV000815713 pathogenic Hereditary breast and ovarian cancer syndrome 2018-08-26 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu2981Lysfs*7) 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 affected with breast cancer (PMID: 26824983). This variant is also known as c.8934delA in the literature. ClinVar contains an entry for this variant (Variation ID: 418600). A different variant (c.8941delG) giving rise to the same protein effect observed here (p.Glu2981Lysfs*7) has been reported in an individual with a personal and/or family history of breast and/or ovarian cancer (PMID: 24156927). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.

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