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
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)
Breast Cancer Information Core (BIC) (BRCA1) RCV000031072 SCV000144552 pathogenic Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
Color RCV000131908 SCV000683064 pathogenic Hereditary cancer-predisposing syndrome 2015-04-01 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
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.
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.
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
Integrated Genetics/Laboratory Corporation of America RCV000047975 SCV000698979 pathogenic Hereditary breast and ovarian cancer syndrome 2017-08-24 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.2806_2809delGATA (p.Asp936Serfs) variant results in a frameshift with a premature termination codon at position 63 of the new reading frame, predicted to result in an absent (due to nonsense-mediated mRNA decay) or truncated protein product, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.2864C>A, p.Ser955X; c.2868delT, p.Gln957fs). One in silico tool predicts a damaging outcome for this variant. The variant was reported in multiple patients with HBOC (e.g. Judkins 2005, Weitzel 2005, Vaca-Paniagua 2012, Rhei 1998, Shattuck-Eidens 1997,Villarreal-Garza 2015). This variant is absent in 121384 control chromosomes, suggesting that it is not a benign, common variant . In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000480052 SCV000296285 pathogenic not provided 2015-03-11 criteria provided, single submitter 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
Sharing Clinical Reports Project (SCRP) RCV000031072 SCV000053668 pathogenic Breast-ovarian cancer, familial 1 2014-04-09 no assertion criteria provided clinical testing

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