ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9401del (p.Gly3134fs) (rs80359759)

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Total submissions: 10
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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) RCV000031822 SCV000301388 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Invitae RCV000045812 SCV000073825 pathogenic Hereditary breast and ovarian cancer syndrome 2018-07-13 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gly3134Alafs*29) 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 the literature in individuals with breast and/or ovarian cancer (PMID: 14531499, 27257965). This variant is also known as 9629delG in the literature. ClinVar contains an entry for this variant (Variation ID: 38239). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Laboratory of Molecular Diagnosis of Cancer,West China Hospital, Sichuan University RCV000240781 SCV000265917 pathogenic Neoplasm of the breast 2015-11-01 criteria provided, single submitter research
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031822 SCV000328125 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV000562878 SCV000666148 pathogenic Hereditary cancer-predisposing syndrome 2017-03-23 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)
Human Genome Sequencing Center Clinical Lab,Baylor College of Medicine RCV000031822 SCV000839916 pathogenic Breast-ovarian cancer, familial 2 2017-05-25 criteria provided, single submitter clinical testing The c.9401del (p.Gly3134Alafs*29) variant in the BRCA2 gene was reported in patients from the Italian Consortium for Hereditary Breast and Ovarian Cancer [PMID 14531499]. This variant has been reported as pathogenic in ClinVar by an expert panel (https://www.ncbi.nlm.nih.gov/clinvar/variation/38239). This one bp deletion in exon 25 results in a frameshift and the creation of a premature stop codon. This variant is thus predicted to result in a loss of function of the protein. This variant has not been observed in the ExAC population database. This variant is thus classified as pathogenic.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000045812 SCV000966963 pathogenic Hereditary breast and ovarian cancer syndrome 2018-07-13 criteria provided, single submitter clinical testing The p.Gly3134AlafsX29 variant in BRCA2 has been reported in multiple families wi th breast and/or ovarian cancer (HBOC; Aretini 2003, Zhong 2016, Rebbeck 2018) a nd was absent from population databases. This variant is predicted to cause a fr ameshift, which alters the protein?s amino acid sequence beginning at position 3 134 and leads to a premature termination codon 29 amino acids downstream. This a lteration is then predicted to lead to a truncated or absent protein. Heterozygo us loss of function of the BRCA2 gene is an established disease mechanism in HBO C. In addition, this variant was classified as Pathogenic on Sept 8, 2016 by the ClinGen-approved ENIGMA expert panel (ClinVar SCV000301388.2). In summary, this variant meets criteria to be classified as pathogenic for HBOC in an autosomal dominant manner based upon absence from controls, proband count, and the predict ed impact on protein. ACMG/AMP Criteria applied: PVS1, PM2, PS4_Supporting.
Sharing Clinical Reports Project (SCRP) RCV000031822 SCV000054430 pathogenic Breast-ovarian cancer, familial 2 2006-04-27 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031822 SCV000147630 pathogenic Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000045812 SCV000588003 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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