ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3008_3009del (p.Asn1002_Phe1003insTer) (rs80357617)

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Total submissions: 12
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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) RCV000077532 SCV000299870 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 RCV000048040 SCV000076053 pathogenic Hereditary breast and ovarian cancer syndrome 2019-10-30 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Phe1003*) 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 an individual affected with breast cancer (PMID: 10644434). This variant is also known as 3127del2 in the literature. ClinVar contains an entry for this variant (Variation ID: 54747). 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 RCV000131913 SCV000186968 pathogenic Hereditary cancer-predisposing syndrome 2019-05-09 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
GeneKor MSA RCV000239209 SCV000296794 pathogenic not specified 2016-07-01 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077532 SCV000325523 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
GeneDx RCV000481473 SCV000566166 pathogenic not provided 2015-03-31 criteria provided, single submitter clinical testing This deletion of 2 nucleotides is denoted BRCA1 c.3008_3009delTT at the cDNA level and p.Phe1003Ter (F1003X) at the protein level. The normal sequence, with the bases that are deleted in brackets, is AACT[TT]GAGG. The deletion creates a nonsense variant, which changes a Phenylalanine to a premature stop codon. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA1 c.3008_3009delTT, also known as 3127_3128delTT using alternate nomenclature, was published as 33127del2 by Wagner et al. (2009) in association with breast and/or ovarian cancer. This variant is considered pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000481473 SCV000888879 pathogenic not provided 2018-02-03 criteria provided, single submitter clinical testing
Color RCV000131913 SCV001352972 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000048040 SCV001360720 pathogenic Hereditary breast and ovarian cancer syndrome 2019-10-04 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.3008_3009delTT (p.Phe1003X) 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 250840 control chromosomes (gnomAD). c.3008_3009delTT has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer (Crawford_2017, Nakamura_2013, Singh_2018, Wen_2017). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Seven submitters, including one expert panel (ENIGMA) have provided clinical-significance assessments for this variant in ClinVar after 2014, and all of them classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Sharing Clinical Reports Project (SCRP) RCV000077532 SCV000109333 pathogenic Breast-ovarian cancer, familial 1 2012-06-06 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000077532 SCV000144607 pathogenic Breast-ovarian cancer, familial 1 2004-02-20 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000048040 SCV000587271 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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