ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.2679_2682del (p.Lys893fs) (rs80357596)

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Total submissions: 14
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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) RCV000031062 SCV000282286 pathogenic Breast-ovarian cancer, familial 1 2016-04-22 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Invitae RCV000047925 SCV000075938 pathogenic Hereditary breast and ovarian cancer syndrome 2018-10-21 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys893Asnfs*106) 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 patients with breast and ovarian cancer (PMID: 9145677, 22006311). It is also known as c.2798delGAAA in the literature. ClinVar contains an entry for this variant (Variation ID: 37481). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000131877 SCV000186932 pathogenic Hereditary cancer-predisposing syndrome 2017-05-05 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)
Counsyl RCV000031062 SCV000220601 likely pathogenic Breast-ovarian cancer, familial 1 2014-08-19 criteria provided, single submitter literature only
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000255129 SCV000296315 pathogenic not provided 2015-03-30 criteria provided, single submitter clinical testing
GeneDx RCV000255129 SCV000321421 pathogenic not provided 2018-09-25 criteria provided, single submitter clinical testing This deletion of 4 nucleotides in BRCA1 is denoted c.2679_2682delGAAA at the cDNA level and p.Lys893AsnfsX106 (K893NfsX106) at the protein level. The normal sequence, with the bases that are deleted in brackets, is TAAA[delGAAA]CAAA. The deletion causes a frameshift, which changes a Lysine to an Asparagine at codon 893, and creates a premature stop codon at position 106 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA1 c.2679_2682delGAAA, previously published as 2798delGAAA, 2798del4 and 2795del4 using alternate nomenclature, was identified in individuals with personal and family histories of breast and/or ovarian cancer with at least one ovarian cancer exhibiting loss of heterozygosity (Couch 1997, Borg 2010, Walsh 2011, Alsop 2012). We consider this variant to be pathogenic.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031062 SCV000325426 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000047925 SCV000605741 pathogenic Hereditary breast and ovarian cancer syndrome 2016-04-28 criteria provided, single submitter clinical testing The p.Lys893fs variant in BRCA1 has been reported in >50 individuals with BRCA1- associated cancers (Couch 1997, Wagner 1998, Borg 2012, Walsh 2011, Lecarpentier 2012, Breast Cancer Information Core (BIC) database) and was absent from large population studies, though the ability of these studies to accurately detect ind els may be limited. This variant is predicted to cause a frameshift, which alter s the protein?s amino acid sequence beginning at position 893 and leads to a pre mature termination codon 106 amino acids downstream. Heterozygous loss of functi on of the BRCA1 gene is an established disease mechanism in individuals with her editary breast and ovarian cancer (HBOC). In summary, this variant meets our cri teria to be classified as pathogenic for HBOC in an autosomal dominant manner.
Color RCV000131877 SCV000683052 pathogenic Hereditary cancer-predisposing syndrome 2015-02-16 criteria provided, single submitter clinical testing
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology RCV000031062 SCV000803347 pathogenic Breast-ovarian cancer, familial 1 2018-05-22 criteria provided, single submitter research
Integrated Genetics/Laboratory Corporation of America RCV000047925 SCV000918689 pathogenic Hereditary breast and ovarian cancer syndrome 2017-11-21 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.2679_2682delGAAA (p.Lys893AsnfsX106) 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. This variant is absent in 245754 control chromosomes (gnomAD). Multiple publications have cited the variant in affected individuals. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Sharing Clinical Reports Project (SCRP) RCV000031062 SCV000053657 pathogenic Breast-ovarian cancer, familial 1 2012-02-13 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000031062 SCV000144509 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 RCV000047925 SCV000587245 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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