ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.2329del (p.Tyr777fs)

dbSNP: rs80357725
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Total submissions: 6
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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) RCV000111826 SCV000299745 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Ambry Genetics RCV000131932 SCV000186988 pathogenic Hereditary cancer-predisposing syndrome 2022-12-09 criteria provided, single submitter clinical testing The c.2329delT pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of one nucleotide at nucleotide position 2329, causing a translational frameshift with a predicted alternate stop codon (p.Y777Mfs*15). This alteration was identified in a large, worldwide study of BRCA1/2 mutation positive families and in a individual who was referred for whole exome sequencing (LaDuca H et al. PLoS ONE, 2017 Feb;12:e0170843; Rebbeck TR et al. Hum. Mutat., 2018 05;39:593-620). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000111826 SCV000325324 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2015-10-02 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000131932 SCV001348865 pathogenic Hereditary cancer-predisposing syndrome 2019-07-22 criteria provided, single submitter clinical testing This variant deletes 1 nucleotide in exon 10 of the BRCA1 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease. Based on available evidence, this variant is classified as Pathogenic.
Invitae RCV001381494 SCV001579915 pathogenic Hereditary breast ovarian cancer syndrome 2022-03-05 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 54536). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr777Metfs*15) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584).
Breast Cancer Information Core (BIC) (BRCA1) RCV000111826 SCV000144381 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2004-02-20 no assertion criteria provided clinical testing

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