Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV003387338 | SCV004098329 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-08-17 | criteria provided, single submitter | clinical testing | The c.299_303dupCCGGG pathogenic mutation, located in coding exon 2 of the CDKN2A gene, results from a duplication of CCGGG at nucleotide position 299, causing a translational frameshift with a predicted alternate stop codon (p.A102Pfs*46). This alteration occurs at the 3' terminus of theCDKN2A gene, is not expected to trigger nonsense-mediated mRNA decay, and only impacts the last 55 amino acids of the protein. However, premature stop codons are typically deleterious in nature, the impacted region is critical for protein function and a significant portion of the protein is affected (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |