ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.3005delA (p.Asn1002Thrfs) (rs80357601)

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Total submissions: 15
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000163096 SCV000213603 pathogenic Hereditary cancer-predisposing syndrome 2018-01-17 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)
Breast Cancer Information Core (BIC) (BRCA1) RCV000019238 SCV000144606 pathogenic Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
Color RCV000163096 SCV000683077 pathogenic Hereditary cancer-predisposing syndrome 2016-11-14 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000019238 SCV000325522 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000019238 SCV000220519 pathogenic Breast-ovarian cancer, familial 1 2014-07-16 criteria provided, single submitter literature only
Department of Medical Genetics,Oslo University Hospital RCV000019238 SCV000564302 pathogenic Breast-ovarian cancer, familial 1 2015-07-01 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000048039 SCV000591418 pathogenic Hereditary breast and ovarian cancer syndrome criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000019238 SCV000299869 pathogenic Breast-ovarian cancer, familial 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000159912 SCV000210031 pathogenic not provided 2018-11-20 criteria provided, single submitter clinical testing This deletion of one nucleotide is denoted BRCA1 c.3005delA at the cDNA level and p.Asn1002ThrfsX22 (N1002TfsX22) at the protein level. The normal sequence, with the bases that are deleted in brackets, is GAAA[delA]CTTT. The deletion causes a frameshift, which changes an Asparagine to a Threonine at codon 1002, and creates a premature stop codon at position 22 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 3005delA, previously reported as 3121delA or 3124delA, has been observed in association with breast and/or ovarian cancer (Simard 1994, Gayther 1999, Borg 2010, Song 2014, Couch 2015). We consider this variant to be pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000048039 SCV000918740 pathogenic Hereditary breast and ovarian cancer syndrome 2018-06-15 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.3005delA (p.Asn1002ThrfsX22) 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 (eg. p.His1006fsX17; p.Ser1009X, p.Pro1010fsX7). The variant was absent in 250362 control chromosomes. c.3005delA has been reported in the literature in multiple individuals affected with Hereditary Breast and Ovarian Cancer. These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Eight clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV000048039 SCV000076052 pathogenic Hereditary breast and ovarian cancer syndrome 2018-11-21 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asn1002Thrfs*22) 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 particular variant has been reported in the literature in individuals with breast and ovarian cancer (PMID: 7894492, 17688236, 20104584, 25452441, 24728189). This variant has also been reported as 3121delA, 3124delA in the literature. ClinVar contains an entry for this variant (Variation ID: 17669). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000019238 SCV000039526 pathogenic Breast-ovarian cancer, familial 1 1994-12-01 no assertion criteria provided literature only
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000159912 SCV000296421 pathogenic not provided 2016-01-09 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000048039 SCV000587270 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000019238 SCV000053675 pathogenic Breast-ovarian cancer, familial 1 2011-12-22 no assertion criteria provided clinical testing

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