ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.2999del (p.Glu1000fs) (rs80357991)

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Total submissions: 8
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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) RCV000083193 SCV000282297 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 RCV000048036 SCV000076049 pathogenic Hereditary breast and ovarian cancer syndrome 2017-04-13 criteria provided, single submitter clinical testing This sequence change deletes 1 nucleotide from exon 10 of the BRCA1 mRNA (c.2999delA), causing a frameshift at codon 1000. This creates a premature translational stop signal (p.Glu1000Glyfs*24) and 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 an individual with family history indicative of a dominantly inherited susceptibility to breast cancer (PMID: 14732925), an individual affected with ovarian cancer (PMID: 21324516) and in individuals in the Breast Cancer Information Core database (PMID: 10923033). This variant is also known as 3118delA in the literature. For these reasons, this variant has been classified as Pathogenic.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000083193 SCV000325519 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
GeneDx RCV000479376 SCV000568135 pathogenic not provided 2018-07-19 criteria provided, single submitter clinical testing This deletion of one nucleotide in BRCA1 is denoted c.2999delA at the cDNA level and p.Glu1000GlyfsX24(E1000GfsX24) at the protein level. The normal sequence, with the base that is deleted in brackets, is CTAG[delA]GGAA. The deletion causes a frameshift, which changes a Glutamic Acid to a Glycine at codon 1000, and creates a premature stop codon at position 24 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.2999delA, also published as 3118delA using alternate nomenclature, has been in association with breast and ovarian cancer (Risch 2006, John 2007, Spearman 2008). We consider this variant to be pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000479376 SCV000600310 pathogenic not provided 2017-03-03 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000083193 SCV000115267 pathogenic Breast-ovarian cancer, familial 1 2012-05-01 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000083193 SCV000144604 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 RCV000048036 SCV000587269 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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