ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.4821_4823delinsC (p.Glu1608fs) (rs587782854)

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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) RCV000241446 SCV000300788 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Ambry Genetics RCV000132458 SCV000187552 pathogenic Hereditary cancer-predisposing syndrome 2015-06-04 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)
GeneDx RCV000255085 SCV000322524 pathogenic not provided 2017-08-01 criteria provided, single submitter clinical testing This combined deletion and insertion is denoted BRCA2 c.4821_4823delTGAinsC at the cDNA level and p.Glu1608AspfsX6 (E1608DfsX6) at the protein level. The surrounding sequence is CTAT[delTGA][insC]GACT. The variant causes a frameshift, which changes a Glutamic Acid to an Aspartic Acid at codon 1608, and creates a premature stop codon at position 6 of the new reading frame. It is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been observed in at least one individual referred for multi-gene panel testing (LaDuca 2017). We consider BRCA2 c.4821_4823delTGAinsC to be pathogenic.
Department of Medical Genetics,Oslo University Hospital RCV000241446 SCV000605684 pathogenic Breast-ovarian cancer, familial 2 2015-07-08 criteria provided, single submitter clinical testing
Color RCV000132458 SCV000683653 pathogenic Hereditary cancer-predisposing syndrome 2015-07-13 criteria provided, single submitter clinical testing
Invitae RCV000496325 SCV000759177 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-30 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu1608Aspfs*6) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs769017108, ExAC 0.002%). This variant has been reported in several families affected with hereditary breast and ovarian cancer (PMID: 29339979). ClinVar contains an entry for this variant (Variation ID: 142963). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000496325 SCV000587724 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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