ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5362dup (p.Ser1788fs) (rs587781849)

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Total submissions: 5
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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) RCV000241452 SCV000300865 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 RCV000130153 SCV000184988 pathogenic Hereditary cancer-predisposing syndrome 2017-09-19 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)
Integrated Genetics/Laboratory Corporation of America RCV000496636 SCV000694865 likely pathogenic Hereditary breast and ovarian cancer syndrome 2016-05-18 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.5362dupT (p.Ser1788Phefs) 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.5386_5387delGA/p.Asp1796fs). One in silico tool predicts a damaging outcome for this variant. This variant is absent in 120684 control chromosomes. In addition, one clinical diagnostic laboratory classified this variant as pathogenic. The variant of interest has not, to our knowledge, been reported in affected individuals via publications; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as likely pathogenic until more information becomes available.
GeneDx RCV000657180 SCV000778901 pathogenic not provided 2017-01-30 criteria provided, single submitter clinical testing This duplication of one nucleotide in BRCA2 is denoted c.5362dupT at the cDNA level and p.Ser1788PhefsX19 (S1788FfsX19) at the protein level. Using alternate nomenclature, this variant would be defined as BRCA2 5590dupT. The normal sequence, with the base that is duplicated in brackets, is GTTTT[dupT]CCAA. The duplication causes a frameshift which changes a Serine to a Phenylalanine at codon 1788, and creates a premature stop codon at position 19 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. We consider this variant to be pathogenic.
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000496636 SCV000587765 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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