ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5692del (p.Asp1898fs) (rs398122539)

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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) RCV000076940 SCV000300917 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 RCV000235464 SCV000293479 pathogenic not provided 2018-01-18 criteria provided, single submitter clinical testing This deletion of one nucleotide in BRCA2 is denoted c.5692delG at the cDNA level and p.Asp1898MetfsX11 (D1898MfsX11) at the protein level. The normal sequence, with the base that is deleted in braces, is ATTG[G]ATGA. The deletion causes a frameshift which changes an Aspartic Acid to a Methionine at codon 1898, and creates a premature stop codon at position 11 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.5692delG, also published as BRCA2 5920delG using alternate nomenclature, has been identified in at least two individuals with a personal or family history of breast and/or ovarian cancer (Dworkin 2009, Churpek 2015). We consider this variant to be pathogenic.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000076940 SCV000327265 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Invitae RCV000461953 SCV000549724 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-11 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asp1898Metfs*11) 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 individuals affected with breast cancer (PMID: 19340607, 25428789). This variant is also known as 5920delG in the literature. ClinVar contains an entry for this variant (Variation ID: 91423). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000461953 SCV000694892 pathogenic Hereditary breast and ovarian cancer syndrome 2017-08-14 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.5692delG (p.Asp1898Metfs) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA2 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.5715dupT, p.Asn1906X; c.5721dupT, p.Leu1908fs). One in silico tool predicts a damaging outcome for this variant. This variant is absent in 120696 control chromosomes but has been reported in the literature in affected individuals. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Sharing Clinical Reports Project (SCRP) RCV000076940 SCV000108737 pathogenic Breast-ovarian cancer, familial 2 2010-09-08 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000461953 SCV000587793 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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