ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.2806_2809del (p.Asp936fs) (rs80357832)

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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) RCV000031072 SCV000299839 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 RCV000047975 SCV000075988 pathogenic Hereditary breast and ovarian cancer syndrome 2018-10-29 criteria provided, single submitter clinical testing This sequence change deletes 4 nucleotides from exon 10 of the BRCA1 mRNA (c.2806_2809delGATA), causing a frameshift at codon 936. This creates a premature translational stop signal (p.Asp936Serfs*63) and is expected to result in an absent or disrupted protein product. Truncating variants in BRCA1 are known to be pathogenic. This particular truncation has been reported in patients with breast and ovarian cancer (PMID: 22722201, 9699640). This variant is also known as 2925del4 in the literature. For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000131908 SCV000186963 pathogenic Hereditary cancer-predisposing syndrome 2017-10-12 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)
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000480052 SCV000296285 pathogenic not provided 2015-03-11 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031072 SCV000325467 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
GeneDx RCV000480052 SCV000566927 pathogenic not provided 2018-09-13 criteria provided, single submitter clinical testing This deletion of four nucleotides in BRCA1 is denoted c.2806_2809delGATA at the cDNA level and p.Asp936SerfsX63 (D936SfsX63) at the protein level. The normal sequence, with the bases that are deleted in brackets, is GAAA[delGATA]AGCC. The deletion causes a frameshift which changes an Aspartic Acid to a Serine at codon 936, and creates a premature stop codon at position 63 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.2806_2809delGATA, also published as BRCA1 2925del4 and BRCA1 c.2805_2808delAGAT using alternate nomenclature, has been reported in association with breast and ovarian cancer and has been reported in Hispanic families (Shattuck-Eidens 1997, Rhei 1998, Weitzel 2005, Vaca-Paniagua 2012, Villarreal-Garza 2015). We consider this variant to be pathogenic.
Color RCV000131908 SCV000683064 pathogenic Hereditary cancer-predisposing syndrome 2015-04-01 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000047975 SCV000698979 pathogenic Hereditary breast and ovarian cancer syndrome 2019-04-01 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.2806_2809delGATA (p.Asp936SerfsX63) 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. (e.g. c.2864C>A, p.Ser955X; c.2868delT, p.Gln957fsX43; c.2934T>G, p.Tyr978X). The variant was absent in 245974 control chromosomes. c.2806_2809delGATA has been reported in the literature in multiple individuals affected with Hereditary Breast and Ovarian Cancer ( (Judkins 2005, Weitzel 2005, Vaca-Paniagua 2012, Rhei 1998, Shattuck-Eidens 1997,Villarreal-Garza 2015). 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. Six clinical diagnostic laboratories and two expert panels (ENIGMA and CIMBA) have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Institute for Biomarker Research,Medical Diagnostic Laboratories, L.L.C. RCV000131908 SCV000747797 pathogenic Hereditary cancer-predisposing syndrome 2018-01-16 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031072 SCV000053668 pathogenic Breast-ovarian cancer, familial 1 2014-04-09 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000031072 SCV000144552 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 RCV000047975 SCV000587255 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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