ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.1499del (p.Gly500fs) (rs397507591)

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Total submissions: 8
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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) RCV000077258 SCV000300434 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077258 SCV000326561 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000496652 SCV000605809 pathogenic Hereditary breast and ovarian cancer syndrome 2016-12-23 criteria provided, single submitter clinical testing The p.Gly500fs variant in BRCA2 has been reported in at least 2 individuals with BRCA2-associated cancers (Meindl 2002) and was absent from large population stu dies. The p.Gly500fs variant is predicted to cause a frameshift, which alters t he protein?s amino acid sequence beginning at position 500 and leads to a premat ure termination codon 9 amino acids downstream. This alteration is then predicte d to lead to a truncated or absent protein. Heterozygous loss of function of the BRCA2 gene is an established disease mechanism in hereditary breast and ovarian cancer (HBOC). In addition, this variant was classified as Pathogenic on Septem ber 8, 2016 by the ClinGen-approved ENIGMA expert panel (ClinVar SCV000300434.2) . In summary, this variant meets criteria to be classified as pathogenic for HBO C in an autosomal dominant manner based upon segregation studies and the predict ed impact to the protein.
Ambry Genetics RCV000565720 SCV000668865 pathogenic Hereditary cancer-predisposing syndrome 2017-09-27 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)
Invitae RCV000496652 SCV000959498 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.Gly500Valfs*9) 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 individuals affected with breast cancer (PMID: 11802209). This variant is also known as 1727delG in the literature. ClinVar contains an entry for this variant (Variation ID: 51135). 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) RCV000077258 SCV000109055 pathogenic Breast-ovarian cancer, familial 2 2009-02-03 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000496652 SCV000587599 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
German Consortium for Hereditary Breast and Ovarian Cancer Center Cologne,University Hospital Cologne RCV000785214 SCV000923782 pathogenic Ovarian Neoplasms 2018-12-01 no assertion criteria provided research

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