ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.2138C>G (p.Ser713Ter) (rs80357233)

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Total submissions: 13
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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) RCV000031032 SCV000299705 pathogenic Breast-ovarian cancer, familial 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Invitae RCV000047730 SCV000075743 pathogenic Hereditary breast and ovarian cancer syndrome 2019-12-01 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser713*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs80357233, ExAC 0.001%). This variant has been observed in individuals with a personal and/or family history of breast and ovarian cancer (PMID: 11139249, 22430266, 21913181). This variant is also known as 2257C>G in the literature. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000074571 SCV000108656 pathogenic not provided 2018-08-03 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA1 c.2138C>G at the cDNA level and p.Ser713Ter (S713X) 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, previously reported as BRCA1 2257C>G using alternate nomenclature, has been reported in association with breast and ovarian cancer (Vaziri 2001, Finkleman 2012, Litton 2012, Monk 2015, Donenberg 2016), and is considered pathogenic.
Ambry Genetics RCV000162851 SCV000213338 pathogenic Hereditary cancer-predisposing syndrome 2019-04-15 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense);Rarity in general population databases (dbsnp, esp, 1000 genomes)
University of Washington Department of Laboratory Medicine, University of Washington RCV000031032 SCV000266027 pathogenic Breast-ovarian cancer, familial 1 2015-11-20 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000074571 SCV000296379 pathogenic not provided 2015-11-18 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031032 SCV000325263 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Department of Medical Genetics, Oslo University Hospital RCV000031032 SCV000564388 pathogenic Breast-ovarian cancer, familial 1 2016-04-21 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000047730 SCV000698921 pathogenic Hereditary breast and ovarian cancer syndrome 2017-02-16 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.2138C>G (p.Ser713X) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA1 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.2157dupA. p.Glu720fsX6; c.2197_2201delGAGAA, p.Glu733fsX5; c.2241delC, p.Asp749fsX4). One in silico tool predicts a damaging outcome for this variant. This variant was found in 1/122388 control chromosomes at a frequency of 0.0000082, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA1 variant (0.0010005). The variant has been reported in numerous affected individuals in the literature. Functional studies have demonstrated a reduction on multiple aspects of BRCA1 function attributed to this variant. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Color RCV000162851 SCV000911170 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031032 SCV000053626 pathogenic Breast-ovarian cancer, familial 1 2012-11-27 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000031032 SCV000144310 pathogenic Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000047730 SCV000587190 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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