ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.2767_2770del (p.Val923fs) (rs80357661)

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Total submissions: 7
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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) RCV000083190 SCV000299833 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 RCV000497271 SCV000210026 pathogenic not provided 2014-05-09 criteria provided, single submitter clinical testing This deletion of 4 nucleotides is denoted BRCA1 c.2767_2770delGTTA at the cDNA level and p.Val923IlefsX76 (V923IfsX76) at the protein level. The normal sequence, with the bases that are deleted in brackets, is GACA[GTTA]ATAT. The deletion causes a frameshift, which changes a Valine to an Isoleucine at codon 923, and creates a premature stop codon at position 76 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. We consider This variant, also known as c.2886_2889delGTTA using alternate nomenclature, to be pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000083190 SCV000296419 pathogenic Breast-ovarian cancer, familial 1 2015-12-23 criteria provided, single submitter clinical testing
Ambry Genetics RCV000564043 SCV000668381 pathogenic Hereditary cancer-predisposing syndrome 2019-03-15 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense);Rarity in general population databases (dbsnp, esp, 1000 genomes)
Integrated Genetics/Laboratory Corporation of America RCV000589720 SCV000698977 pathogenic Hereditary breast and ovarian cancer syndrome 2019-01-28 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.2767_2770delGTTA (p.Val923IlefsX76) 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 (e.g. c.2806_2809delGATA (p.Asp936fsX63), c.2864C>A (p.Ser955X), and c.2868delT (p.Gln957fsX43)). The variant allele was found at a frequency of 4.1e-06 in 245770 control chromosomes (gnomAD). c.2767_2770delGTTA has been reported in the literature in individuals affected with tumors that belong to the Hereditary Breast and Ovarian Cancer (HBOC) syndrome tumor spectrum (Pritchard 2016, Susswein 2015, and in the BIC database). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three 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.
Sharing Clinical Reports Project (SCRP) RCV000083190 SCV000115264 pathogenic Breast-ovarian cancer, familial 1 2012-03-14 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000083190 SCV000144542 pathogenic Breast-ovarian cancer, familial 1 2002-06-20 no assertion criteria provided clinical testing

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