ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.5050_5051del (p.Thr1684fs)

dbSNP: rs879255283
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Total submissions: 5
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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) RCV000239167 SCV000300192 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000239167 SCV000296433 likely pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2016-03-05 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000239167 SCV000326120 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2015-10-02 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000539566 SCV000636005 pathogenic Hereditary breast ovarian cancer syndrome 2024-10-08 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Thr1684Tyrfs*10) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with BRCA1-related conditions (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 252385). RNA analysis performed to evaluate the impact of this premature translational stop signal on mRNA splicing indicates it does not significantly alter splicing (internal data). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000565393 SCV000661123 pathogenic Hereditary cancer-predisposing syndrome 2021-08-09 criteria provided, single submitter clinical testing The c.5050_5051delAC pathogenic mutation, located in coding exon 15 of the BRCA1 gene, results from a deletion of two nucleotides at nucleotide positions 5050 to 5051, causing a translational frameshift with a predicted alternate stop codon (p.T1684Yfs*10). This alteration was identified in a large, worldwide study of BRCA1/2 mutation positive families (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.

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