ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.3689del (p.Ser1230fs) (rs80359398)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000219035 SCV000885094 pathogenic not provided 2018-02-14 criteria provided, single submitter clinical testing The BRCA2 c.3689delC: p.Ser1230fs variant (rs80359398), also known as 3917delC, is published in the medical literature in individuals with pancreatic or ovarian cancer (Lucas 2014, Song 2014). The variant is listed as pathogenic by several sources in the ClinVar database (Variation ID: 37853), but is not listed in the population databases (1000 Genomes Project, Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. This variant deletes one nucleotide, causes a frameshift, and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Considering available information, this variant is classified as pathogenic. References: Lucas AL et al. BRCA1 and BRCA2 germline mutations are frequently demonstrated in both high-risk pancreatic cancer screening and pancreatic cancer cohorts. Cancer. 2014 Jul 1;120(13):1960-7. Song H et al. The contribution of deleterious germline mutations in BRCA1, BRCA2 and the mismatch repair genes to ovarian cancer in the population. Hum Mol Genet. 2014 Sep 1;23(17):4703-9.
Ambry Genetics RCV000129939 SCV000184758 pathogenic Hereditary cancer-predisposing syndrome 2017-10-13 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)
Breast Cancer Information Core (BIC) (BRCA2) RCV000031434 SCV000146280 pathogenic Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Color RCV000129939 SCV000910927 pathogenic Hereditary cancer-predisposing syndrome 2016-05-23 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031434 SCV000326896 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031434 SCV000282381 pathogenic Breast-ovarian cancer, familial 2 2016-04-22 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000219035 SCV000278847 pathogenic not provided 2018-10-31 criteria provided, single submitter clinical testing This deletion of one nucleotide in BRCA2 is denoted c.3689delC at the cDNA level and p.Ser1230LeufsX9 (S1230LfsX9) at the protein level. The normal sequence, with the base that is deleted in brackets, is GTTT[delC]TACT. The deletion causes a frameshift, which changes a Serine to a Leucine at codon 1230 and creates a premature stop codon at position 9 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Also published as 3917delC using alternate nomenclature, BRCA2 c.3689delC has been observed in at least two individuals with a personal and/or family history of breast, ovarian, or pancreatic cancer (Melchor 2007, Lucas 2014, Song 2014, Copson 2018). This variant has also been observed in an individual with a family history of breast and/or ovarian cancer as well as colorectal cancer, who also carried a BRCA1 frameshift variant (Dobbins 2016). We consider this variant to be pathogenic.
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology RCV000031434 SCV000803345 pathogenic Breast-ovarian cancer, familial 2 2018-02-27 criteria provided, single submitter research
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000031434 SCV000296567 pathogenic Breast-ovarian cancer, familial 2 2016-03-01 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000219035 SCV000889027 pathogenic not provided 2016-03-01 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000496853 SCV000587677 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000031434 SCV000054039 pathogenic Breast-ovarian cancer, familial 2 2012-04-03 no assertion criteria provided clinical testing

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