ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.2339C>G (p.Ser780Ter) (rs587781471)

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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) RCV000241405 SCV000300510 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Ambry Genetics RCV000129415 SCV000184185 pathogenic Hereditary cancer-predisposing syndrome 2016-05-02 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)
GeneKor MSA RCV000484555 SCV000296816 pathogenic not provided 2017-11-01 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000241405 SCV000326692 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
GeneDx RCV000484555 SCV000568457 pathogenic not provided 2016-09-09 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.2339C>G at the cDNA level and p.Ser780Ter (S780X) at the protein level. Using alternate nomenclature, this variant would be defined as BRCA2 c.2567C>G. 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 has been reported in association with breast and/or ovarian cancer (Konstantopoulou 2014, Kwong 2016, Couch 2015) and is considered pathogenic.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000508058 SCV000605781 pathogenic Hereditary breast and ovarian cancer syndrome 2015-07-29 criteria provided, single submitter clinical testing The p.Ser780X variant in BRCA2 has been reported in 2 individuals with breast ca ncer (1 male and 1 female; Konstantopoulou 2014, Couch 2015), and was absent fro m large population studies. This nonsense variant leads to a premature terminati on codon at position 780, which is predicted to lead to a truncated or absent pr otein. Heterozygous loss of function of the BRCA2 gene is an established disease mechanism in hereditary breast and ovarian cancer (HBOC). In summary, this vari ant meets our criteria to be classified as pathogenic for HBOC in an autosomal d ominant manner based upon predicted impact to the protein and absence in control s.
Invitae RCV000508058 SCV000635216 pathogenic Hereditary breast and ovarian cancer syndrome 2018-10-22 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 780 (p.Ser780*) 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 families affected with breast and/or ovarian cancer (PMID: 24010542, 27157322). For these reasons, this variant has been classified as Pathogenic.
Counsyl RCV000241405 SCV000677758 pathogenic Breast-ovarian cancer, familial 2 2017-02-21 criteria provided, single submitter clinical testing

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