Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000570486 | SCV000669201 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-04-19 | criteria provided, single submitter | clinical testing | The p.Y44* pathogenic mutation (also known as c.132C>G), located in coding exon 1 of the CDKN2A gene, results from a C to G substitution at nucleotide position 132. This changes the amino acid from a tyrosine to a stop codon within coding exon 1. A different nucleotide substitution (c.132C>A) resulting in the same stop codon (p.Y44*) was identified in several melanoma families (MacKie RM et al. J. Invest. Dermatol. 1998 Aug;111(2):269-72; Begg CB et al. J. Natl. Cancer Inst. 2005 Oct;97(20):1507-15). Another alteration (c.131_132insAA) also resulting in the same stop codon (p.Y44*) was reported in a patient with multiple primary cutaneous melanomas (de Snoo FA et al. J. Am. Acad. Dermatol. 2007 May;56(5):748-52). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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. |
| Color Diagnostics, |
RCV000570486 | SCV000689579 | pathogenic | Hereditary cancer-predisposing syndrome | 2017-08-04 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001382593 | SCV001581434 | pathogenic | Familial melanoma | 2024-01-12 | 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 not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with melanoma (PMID: 9699728, 16234564, 17276542, 29661971). ClinVar contains an entry for this variant (Variation ID: 483337). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| Clinical Genetics Laboratory, |
RCV004696949 | SCV005197433 | pathogenic | not provided | 2023-03-31 | criteria provided, single submitter | clinical testing |