ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.1147del (p.Ile383fs) (rs80359265)

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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) RCV000112884 SCV000300388 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 RCV000112884 SCV000326503 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV000562743 SCV000661400 pathogenic Hereditary cancer-predisposing syndrome 2018-03-21 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)
Color RCV000562743 SCV000683403 pathogenic Hereditary cancer-predisposing syndrome 2016-11-28 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000112884 SCV000744402 pathogenic Breast-ovarian cancer, familial 2 2015-09-21 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000825612 SCV000966964 pathogenic Hereditary breast and ovarian cancer syndrome 2018-10-21 criteria provided, single submitter clinical testing The p.Ile383SerfsX16 variant in BRCA2 has been reported in 1 individual with her editary breast and/or ovarian cancer (HBOC; Breast cancer information core (BIC) : https://research.nhgri.nih.gov/bic/) and in 2 individuals with a personal and/ or family history of HBOC (van der Hout 2006). It was absent from large populati on studies. This variant is predicted to cause a frameshift, which alters the pr otein?s amino acid sequence beginning at position 383 and leads to a premature t ermination codon 16 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Heterozygous loss of function of the BRC A2 gene is an established disease mechanism in individuals with HBOC. Additional ly, this variant was classified as pathogenic on Sept 8, 2016 by the ClinGen-app roved ENIGMA expert panel (ClinVar SCV000300388.2). In summary, this variant mee ts criteria to be classified as pathogenic for HBOC in an autosomal dominant man ner based on its presence in multiple affected individuals, absence from the gen eral population and the predicted impact on the protein. ACMG/AMP Criteria appli ed: PVS1, PM2, PS4_Supporting.
Breast Cancer Information Core (BIC) (BRCA2) RCV000112884 SCV000145821 pathogenic Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000112884 SCV000733223 pathogenic Breast-ovarian cancer, familial 2 no assertion criteria provided clinical testing

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