ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.4889C>G (p.Ser1630Ter) (rs80358711)

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Total submissions: 14
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131080 SCV000186010 pathogenic Hereditary cancer-predisposing syndrome 2017-12-14 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) RCV000077340 SCV000146499 pathogenic Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Color RCV000131080 SCV000537669 pathogenic Hereditary cancer-predisposing syndrome 2015-04-06 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077340 SCV000327100 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000077340 SCV000677680 pathogenic Breast-ovarian cancer, familial 2 2017-01-04 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000255089 SCV000225188 pathogenic not provided 2016-11-04 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000077340 SCV000300794 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000255089 SCV000321464 pathogenic not provided 2019-01-16 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA2 c.4889C>G at the cDNA level and p.Ser1630Ter (S1630X) at the protein level. The substitution creates a nonsense variant, which changes a Serine to a premature stop codon (TCA>TGA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant, also known as BRCA2 5117C>G using alternate nomenclature, has been reported in individuals and families with breast and/or ovarian cancer (Ozcelik 2003, Claus 2005, Malone 2006, Rodriguez 2012, Castera 2014, Zugazagoitia 2014, Pellegrino 2016). We consider this variant to be pathogenic.
GeneKor MSA RCV000255089 SCV000693568 pathogenic not provided 2017-11-01 criteria provided, single submitter clinical testing
Invitae RCV000044512 SCV000072525 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-07 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 1630 (p.Ser1630*) of the BRCA2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA2 are known to be pathogenic. This particular variant has been reported in the literature in families and individuals affected with breast cancer (PMID: 12920083, 22762150, 17624602). This variant is also known as 5117C>G in the literature. For these reasons, this variant has been classified as Pathogenic.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000044512 SCV000605799 pathogenic Hereditary breast and ovarian cancer syndrome 2016-10-04 criteria provided, single submitter clinical testing The p.Ser1630X variant in BRCA2 has been reported in at least 15 individuals wit h BRCA2-associated cancers (Castera 2014, Castro 2013, Lecarpentier 2012, Ozceli k 2003, Zugazagoitia 2014, Breast Cancer Information Core database, www.research .nhgri.nih.gov/bic/). This variant has been identified in 2/65832 European chrom osomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org ; dbSNP rs80358711). This frequency is low enough to be consistent with the freq uency of hereditary breast and ovarian cancer (HBOC) in the general population. This nonsense variant leads to a premature termination codon at position 1630, w hich is predicted to lead to a truncated or absent protein. Heterozygous loss of function of the BRCA2 gene is an established disease mechanism in HBOC. In addi tion, this variant was classified as Pathogenic on September 8, 2016 by the Clin Gen-approved ENIGMA expert panel (ClinVar SCV000300794.2). In summary, this vari ant meets criteria to be classified as pathogenic for HBOC in an autosomal domin ant manner based upon the predicted impact to the protein.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000077340 SCV000296626 pathogenic Breast-ovarian cancer, familial 2 2015-08-21 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000044512 SCV000587730 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000077340 SCV000109137 pathogenic Breast-ovarian cancer, familial 2 2011-02-08 no assertion criteria provided clinical testing

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