ClinVar Miner

Submissions for variant NM_000077.5(CDKN2A):c.106del (p.Ala36fs)

dbSNP: rs398123152
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001524193 SCV001733971 pathogenic Hereditary cancer-predisposing syndrome 2020-12-21 criteria provided, single submitter clinical testing This variant deletes 1 nucleotide in exon 1 of the CDKN2A (p16INK4A) gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, this variant has not been reported in individuals affected with hereditary cancer in the literature. 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 (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Ambry Genetics RCV001524193 SCV005032100 pathogenic Hereditary cancer-predisposing syndrome 2024-03-05 criteria provided, single submitter clinical testing The c.106delG pathogenic mutation, located in coding exon 1 of the CDKN2A gene, results from a deletion of one nucleotide at nucleotide position 106, causing a translational frameshift with a predicted alternate stop codon (p.A36Rfs*17). This variant was identified in a family meeting clinical criteria for melanoma-pancreatic cancer syndrome. Specifically, the proband was affected with head and neck squamous cell carcinoma and cutaneous melanoma at 48 and 43 years old, respectively (Cabanillas R et al. Head Neck, 2013 Mar;35:E80-4). Multiple other affected individuals of Spanish ancestry have also tested positive for this mutation (Potrony M et al. J Am Acad Dermatol, 2014 Nov;71:888-95; Puig S et al. Genet Med, 2016 Jul;18:727-36). 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.

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