ClinVar Miner

Submissions for variant NM_000077.5(CDKN2A):c.44G>A (p.Trp15Ter)

dbSNP: rs876658556
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000220239 SCV000273966 pathogenic Hereditary cancer-predisposing syndrome 2022-01-05 criteria provided, single submitter clinical testing The p.W15* pathogenic mutation (also known as c.44G>A), located in coding exon 1 of the CDKN2A gene, results from a G to A substitution at nucleotide position 44. This changes the amino acid from a tryptophan to a stop codon within coding exon 1. This alteration has been previously described in two melanoma kindreds as well as a patient diagnosed with pancreatic cancer (FitzGerald MG et al. Proc. Natl. Acad. Sci. U.S.A. 1996 Aug;93:8541-5; Bishop DT et al. J. Natl. Cancer Inst. 2002 Jun;94:894-903; Yurgelun MB et al. Genet Med. 2019 01;21:213-223). 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000685369 SCV000812847 pathogenic Familial melanoma 2023-10-22 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp15*) 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: 8710906, 10398427, 12072543, 15146471, 28830827). ClinVar contains an entry for this variant (Variation ID: 230421). For these reasons, this variant has been classified as Pathogenic.

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