ClinVar Miner

Submissions for variant NM_000077.5(CDKN2A):c.47_50del (p.Leu16fs)

dbSNP: rs587782206
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130872 SCV000185774 pathogenic Hereditary cancer-predisposing syndrome 2022-04-21 criteria provided, single submitter clinical testing The c.47_50delTGGC pathogenic mutation, located in coding exon 1 of the CDKN2A gene, results from a deletion of 4 nucleotides at nucleotide positions 47 to 50, causing a translational frameshift with a predicted alternate stop codon (p.L16Pfs*9). This pathogenic mutation has been reported in an individual diagnosed with multiple primary melanomas beginning at age 40 and whose father had pancreatic cancer (Wadt KA et al. PLoS ONE. 2015 Mar;10:e0122662). 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 RCV000458116 SCV000545505 pathogenic Familial melanoma 2024-01-10 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu16Profs*9) 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 multiple primary melanomas (PMID: 25803691). ClinVar contains an entry for this variant (Variation ID: 142061). For these reasons, this variant has been classified as Pathogenic.
Faculté Pluridciplinaire Nador, Université Mohamed Premier RCV001250938 SCV001250921 likely pathogenic Squamous cell lung carcinoma 2020-05-05 no assertion criteria provided clinical testing

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