ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.4731delA (p.Glu1577Aspfs) (rs397507740)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000570296 SCV000668671 pathogenic Hereditary cancer-predisposing syndrome 2016-06-15 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)
Counsyl RCV000239279 SCV000677825 likely pathogenic Breast-ovarian cancer, familial 2 2017-04-10 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000239279 SCV000783816 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 RCV000657227 SCV000778953 pathogenic not provided 2017-01-18 criteria provided, single submitter clinical testing This deletion of one nucleotide in BRCA2 is denoted c.4731delA at the cDNA level and p.Glu1577AspfsX2 (E1577DfsX2) at the protein level. The normal sequence, with the base that is deleted in brackets, is TTGA[delA]TTAG. The deletion causes a frameshift which changes a Glutamic Acid to an Aspartic Acid at codon 1577, and creates a premature stop codon at position 2 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.4731delA, previously reported as BRCA2 4959delA using alternate nomenclature, as been observed in at least one individual with triple negative breast cancer and a family history of breast and ovarian cancer (Churpek 2015). We consider this variant to be pathogenic.
Invitae RCV000530337 SCV000635400 pathogenic Hereditary breast and ovarian cancer syndrome 2018-01-02 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu1577Aspfs*2) 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 an individual affected with breast cancer (PMID: 25428789). ClinVar contains an entry for this variant (Variation ID: 252834). 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) RCV000239279 SCV000297437 pathogenic Breast-ovarian cancer, familial 2 2008-08-13 no assertion criteria provided clinical testing

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