ClinVar Miner

Submissions for variant NM_007299.4(BRCA1):c.787+1248A>T (rs80357082)

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Total submissions: 19
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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) RCV000077505 SCV000299687 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 RCV000047689 SCV000075702 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-27 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys679*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the literature in many individuals affected with breast and/or ovarian cancer (PMID: 21913181, 9333265, 22006311, 24504028, 26681312), as well as an individual affected with fallopian tube cancer (PMID: 11810084). This variant is also known as 2154A>T in the literature. ClinVar contains an entry for this variant (Variation ID: 54442). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000074569 SCV000108654 pathogenic not provided 2018-04-17 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA1 c.2035A>T at the cDNA level and p.Lys679Ter (K679X) at the protein level. The substitution creates a nonsense variant, changing a Lysine to a premature stop codon (AAG>TAG). This variant, also published as BRCA1 2154A>T using alternate nomenclature, is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA1 Lys679Ter has been reported in association with Hereditary Breast and Ovarian Cancer syndrome (Shattuck-Eidens 1997, Hébert-Blouin 2002, Pal 2005, Walsh 2011, Cunningham 2014) and is considered to be pathogenic.
Ambry Genetics RCV000131904 SCV000186959 pathogenic Hereditary cancer-predisposing syndrome 2017-05-12 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)
University of Washington Department of Laboratory Medicine,University of Washington RCV000077505 SCV000266037 pathogenic Breast-ovarian cancer, familial 1 2015-11-20 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000074569 SCV000296347 pathogenic not provided 2015-05-28 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077505 SCV000325216 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Color RCV000131904 SCV000537668 pathogenic Hereditary cancer-predisposing syndrome 2016-05-02 criteria provided, single submitter clinical testing
Department of Pathology and Molecular Medicine,Queen's University RCV000047689 SCV000588036 pathogenic Hereditary breast and ovarian cancer syndrome 2017-04-20 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000047689 SCV000591364 pathogenic Hereditary breast and ovarian cancer syndrome 2014-12-10 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000506031 SCV000602719 pathogenic not specified 2017-05-05 criteria provided, single submitter clinical testing
Counsyl RCV000077505 SCV000677640 pathogenic Breast-ovarian cancer, familial 1 2015-07-02 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000047689 SCV000698910 pathogenic Hereditary breast and ovarian cancer syndrome 2017-07-23 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.2035A>T (p.Lys679X) 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.2071delA, p.Arg691fsX10; c.2138C>G, p.Ser713X; c.2157dupA, p.Glu720fsX6). One in silico tool predicts a damaging outcome for this variant. This variant is absent in 124422 control chromosomes and has been reported in the literature in numerous breast and ovarian cancer patients. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Human Genome Sequencing Center Clinical Lab,Baylor College of Medicine RCV000077505 SCV000839883 pathogenic Breast-ovarian cancer, familial 1 2017-05-10 criteria provided, single submitter clinical testing The c.2035A>T (p.Lys679*) variant in the BRCA1 gene has been reported in multiple patients with breast and/or ovarian cancer [PMID 9333265, 24504028, 11810084, 22006311]. This change was also reported in 34 patients in the Breast Cancer Information Core database. This c.2035A>T (p.Lys679*) variant creates a premature stop codon at amino acid position 679 of the BRCA1 protein and is thus predicted to result in a loss of function of the protein. The c.2035A>T (p.Lys679*) variant has not been reported in the ExAC database. This variant is thus classified as pathogenic.
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000735497 SCV000901141 pathogenic Breast and/or ovarian cancer 2016-10-05 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077505 SCV000109305 pathogenic Breast-ovarian cancer, familial 1 2013-03-18 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000077505 SCV000144279 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 RCV000047689 SCV000587180 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735497 SCV000863635 pathogenic Breast and/or ovarian cancer 2000-06-30 no assertion criteria provided clinical testing

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