Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV003171491 | SCV003856750 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-11-01 | criteria provided, single submitter | clinical testing | The c.97-4_104del12 pathogenic mutation results from a deletion of 12 nucleotides between positions c.97-4 and c.104 and involves the canonical splice acceptor site before coding exon 3 of the TP53 gene. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site. The stop codon in the predicted resulting transcript occurs in the 5' end ofthe TP53 gene. As such, this alteration may escape nonsense-mediated mRNAdecay and/or be prone to rescue by re-initiation (Rivas et al. Science. 2015 May 8;348(6235):666-9; Lindeboom et al. Nat Genet. 2016 Oct;48(10):1112-8; Rhee et al. Sci Rep. 2017 May 10;7(1):1653). The exact functional effect of this alteration is unknown; however, the impacted region is critical for protein function (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). As such, this alteration is interpreted as a disease-causing mutation. |