Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000493771 | SCV000581511 | pathogenic | Hereditary cancer-predisposing syndrome | 2024-01-23 | criteria provided, single submitter | clinical testing | The c.132delC pathogenic mutation, located in coding exon 1 of the CDKN2A gene, results from a deletion of one nucleotide at nucleotide position 132, causing a translational frameshift with a predicted alternate stop codon (p.Y44*). This mutation and others causing protein truncation at the same position have been identified in families with multiple melanomas and pancreatic cancer (MacKie RM et al. J. Invest. Dermatol., 1998 Aug;111:269-72; Orlow I et al. J. Invest. Dermatol., 2007 May;127:1234-43; Soura E et al. J. Am. Acad. Dermatol., 2016 Mar;74:395-407; quiz 408-10). 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. |
| Labcorp Genetics |
RCV000638987 | SCV000760545 | pathogenic | Familial melanoma | 2023-08-11 | criteria provided, single submitter | clinical testing | This premature translational stop signal has been observed in individual(s) with melanoma and pancreatic cancer (PMID: 18363633, 26892650). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr44*) in the CDKN2A (p16INK4a) gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CDKN2A (p16INK4a) are known to be pathogenic (PMID: 15146471, 16905682). ClinVar contains an entry for this variant (Variation ID: 429111). For these reasons, this variant has been classified as Pathogenic. |
| Color Diagnostics, |
RCV000493771 | SCV001356643 | pathogenic | Hereditary cancer-predisposing syndrome | 2019-12-14 | criteria provided, single submitter | clinical testing | This variant deletes 1 nucleotide in exon 1 of the CDKN2A gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has been observed in two individuals who each had two or more primary melanomas (PMID: 18363633, 26892650) and in the mother of one proband who was affected with pancreatic cancer (PMID: 26892650). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of CDKN2A function is a known mechanism of disease. Based on the available evidence, this variant is classified as Pathogenic. |