ClinVar Miner

Submissions for variant NM_000077.5(CDKN2A):c.70C>G (p.Arg24Gly)

dbSNP: rs761014328
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001988360 SCV002269970 uncertain significance Familial melanoma 2023-05-09 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 1481554). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the p.Arg24 amino acid residue in CDKN2A (p16INK4a). Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 8570179, 9699728, 10390011, 11595726, 15146471, 15945100, 16905682, 18843795, 20340136, 23190892). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant  is likely to be tolerated. This variant has not been reported in the literature in individuals affected with CDKN2A (p16INK4a)-related conditions. This variant is present in population databases (rs761014328, gnomAD 0.002%). This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 24 of the CDKN2A (p16INK4a) protein (p.Arg24Gly).
Ambry Genetics RCV004946981 SCV005559312 uncertain significance Hereditary cancer-predisposing syndrome 2024-09-13 criteria provided, single submitter clinical testing The p.R24G variant (also known as c.70C>G), located in coding exon 1 of the CDKN2A gene, results from a C to G substitution at nucleotide position 70. The arginine at codon 24 is replaced by glycine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.

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