ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.2563C>T (p.Gln855Ter) (rs80357131)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000223464 SCV000277957 pathogenic Hereditary cancer-predisposing syndrome 2016-08-30 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) (BRCA1) RCV000031056 SCV000144475 pathogenic Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031056 SCV000325398 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031056 SCV000299786 pathogenic Breast-ovarian cancer, familial 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000657621 SCV000779364 pathogenic not provided 2018-10-02 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.2563C>T at the cDNA level and p.Gln855Ter (Q855X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAG>TAG), 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 cancer (Lalloo 2003, Perkowska 2003) and is considered pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000047880 SCV000916768 pathogenic Hereditary breast and ovarian cancer syndrome 2017-12-04 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.2563C>T (p.Gln855X) 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. p.Ser955X, p.Glu1017X, p.Leu1086X etc.). This variant is absent in 245796 control chromosomes (gnomAD). It has been reported in several HBOC patients/families in literature and clinical databases, including two patients who had early onset breast cancer. Several clinical diagnostic laboratories/reputable databases have classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000047880 SCV000075893 pathogenic Hereditary breast and ovarian cancer syndrome 2016-10-11 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 855 (p.Gln855*) of the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic. This particular variant has been reported in the literature in a family affected with breast cancer (PMID: 12673801). This variant is also known as 2682C>T in the literature. For these reasons, this variant has been classified as Pathogenic.
Michigan Medical Genetics Laboratories,University of Michigan RCV000031056 SCV000195907 pathogenic Breast-ovarian cancer, familial 1 2014-11-03 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000031056 SCV000296402 pathogenic Breast-ovarian cancer, familial 1 2015-10-28 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000657621 SCV000887643 pathogenic not provided 2015-10-28 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000047880 SCV000587232 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000031056 SCV000053651 pathogenic Breast-ovarian cancer, familial 1 2012-10-08 no assertion criteria provided clinical testing

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