Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000565411 | SCV000669200 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-08-13 | criteria provided, single submitter | clinical testing | The c.131dupA pathogenic mutation, located in coding exon 1 of the CDKN2A gene, results from a duplication of A at nucleotide position 131. This changes the amino acid from a tyrosine to a stop codon within coding exon 1 (p.Y44*). This alteration has been reported in multiple individuals with personal and family histories of cutaneous melanoma (Begg CB et al. J. Natl. Cancer Inst. 2005 Oct;97(20):1507-15; Potrony M et al. J Am Acad Dermatol. 2014 Nov;71(5):888-95). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Of note, this alteration is also designated c.131_132insA in published literature. 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 |
RCV000698266 | SCV000826921 | pathogenic | Familial melanoma | 2023-11-25 | criteria provided, single submitter | clinical testing | 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). This variant is present in population databases (rs730881673, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with melanoma (PMID: 16234564, 17218939, 26681309). This variant is also known as c.131_132insA. ClinVar contains an entry for this variant (Variation ID: 483336). For these reasons, this variant has been classified as Pathogenic. |
| Gene |
RCV003441953 | SCV004168482 | pathogenic | not provided | 2023-04-25 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25064638, 27161972, 35706071, 26907448, 31856090, 35810469, 16234564, 9699728, 17218939, 32482799, 26681309, 25356972, 29922827) |
| Baylor Genetics | RCV004569210 | SCV005057245 | pathogenic | Melanoma and neural system tumor syndrome | 2024-02-03 | criteria provided, single submitter | clinical testing |