ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.2989_2990dup (p.Asn997fs) (rs80357829)

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Total submissions: 13
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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) RCV000143831 SCV000299866 pathogenic Breast-ovarian cancer, familial 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Ambry Genetics RCV000164310 SCV000214941 pathogenic Hereditary cancer-predisposing syndrome 2018-01-24 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)
GeneDx RCV000237066 SCV000292515 pathogenic not provided 2015-06-10 criteria provided, single submitter clinical testing This duplication of 2 nucleotides in BRCA1 is denoted c.2989_2990dupAA at the cDNA level and p.Asn997LysfsX4 (N997KfsX4) at the protein level. The normal sequence, with the bases that are duplicated in braces, is GAAA[AA]TCTG. The duplication causes a frameshift, which changes an Asparagine to a Lysine at codon 997, and creates a premature stop codon at position 4 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.2989_2990dupAA, also reported as BRCA1 c.2990_2991insAA, 3108insAA, 3108_3109dupAA, or 3109insAA using alternate nomenclature, has been reported in families with multiple cases of breast and/or ovarian cancer and individuals with epithelial ovarian or fallopian tube cancers (Peelen 1997, Norquist 2010, Song 2014, Cunningham 2014). We consider this variant to be pathogenic.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000143831 SCV000325516 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Department of Medical Genetics,Oslo University Hospital RCV000143831 SCV000564359 pathogenic Breast-ovarian cancer, familial 1 2015-03-30 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000143831 SCV000743409 pathogenic Breast-ovarian cancer, familial 1 2014-10-10 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000143831 SCV000744642 pathogenic Breast-ovarian cancer, familial 1 2015-09-21 criteria provided, single submitter clinical testing
Human Genome Sequencing Center Clinical Lab,Baylor College of Medicine RCV000143831 SCV000839897 pathogenic Breast-ovarian cancer, familial 1 2017-05-25 criteria provided, single submitter clinical testing The c.2989_2990dup (p.Asn997Lysfs*4) variant in the BRCA1 gene has been detected multiple patients with breast cancer and/or ovarian cancer [PMID 9150151, 24504028]. This variant is considered a founder mutation among the Dutch and Belgium populations [PMID 9150151]. This 2 bp duplication in exon 10 results in a frameshift and the creation of a premature stop codon. This variant is thus predicted to result in a loss of function of the protein. This variant has not been detected in the ExAC database. This variant thus classified as pathogenic.
Color RCV000164310 SCV000909327 pathogenic Hereditary cancer-predisposing syndrome 2018-03-27 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000143831 SCV000053673 pathogenic Breast-ovarian cancer, familial 1 2010-08-17 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000143831 SCV000144598 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 RCV000496906 SCV000587268 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000143831 SCV000733632 pathogenic Breast-ovarian cancer, familial 1 no assertion criteria provided clinical testing

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