ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.2864C>A (p.Ser955Ter) (rs80357295)

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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) RCV000077530 SCV000299845 pathogenic Breast-ovarian cancer, familial 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Ambry Genetics RCV000131912 SCV000186967 pathogenic Hereditary cancer-predisposing syndrome 2018-09-07 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
GeneDx RCV000255164 SCV000321424 pathogenic not provided 2016-11-07 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA1 c.2864C>A at the cDNA level and p.Ser955Ter (S955X) at the protein level. The substitution, also known as 2983C>A using alternate nomenclature, creates a nonsense variant, which changes a Serine to a premature stop codon (TCA>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been observed in multiple individuals with personal and/or family history of breast and/or ovarian cancer, and has been reported as a recurrent pathogenic variant in the Hispanic population (Weitzel 2005, Vogel 2007, Thomassen 2008, Vaidyanathan 2009, Borg 2010, Fackenthal 2012). We consider this variant to be pathogenic.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077530 SCV000325481 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000077530 SCV000488025 pathogenic Breast-ovarian cancer, familial 1 2015-12-28 criteria provided, single submitter clinical testing
Department of Medical Genetics, Oslo University Hospital RCV000077530 SCV000564361 pathogenic Breast-ovarian cancer, familial 1 2015-04-21 criteria provided, single submitter clinical testing
Color RCV000131912 SCV000688406 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000255164 SCV000888874 pathogenic not provided 2017-08-14 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000496521 SCV001362815 pathogenic Hereditary breast and ovarian cancer syndrome 2019-07-15 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.2864C>A (p.Ser955X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the 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. The variant was absent in 251560 control chromosomes. c.2864C>A has been reported in the literature in multiple individuals affected with Hereditary Breast and Ovarian Cancer (including Borg_2010, Fackenthal_2012, Heramb_2018, Litton_2011, Thomassen_2008, Vaidyanathan_2009, Vogel_2007, Weitzel_2005). These data indicate that the variant is very likely to be associated with disease. Eight clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Sharing Clinical Reports Project (SCRP) RCV000077530 SCV000109331 pathogenic Breast-ovarian cancer, familial 1 2011-09-14 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000077530 SCV000144563 pathogenic Breast-ovarian cancer, familial 1 2004-02-20 no assertion criteria provided clinical testing
Pathway Genomics RCV000077530 SCV000207334 pathogenic Breast-ovarian cancer, familial 1 2014-11-06 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000496521 SCV000587258 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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