Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000492216 | SCV000581117 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-12-05 | criteria provided, single submitter | clinical testing | The c.86_96+4del15 pathogenic mutation results from a deletion of 15 nucleotides spanning the last 11 nucleotides of coding exon 2 through the first 4 nucleotides after coding exon 2 in the TP53 gene. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration also causes an out-of-frame deletion of 11 nucleotides between positions 86 and 96 within coding exon 2, resulting in a translational frameshift with a predicted alternate stop codon. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, and frameshifts are 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. |