ClinVar Miner

Submissions for variant NM_000077.5(CDKN2A):c.225C>G (p.Pro75=)

gnomAD frequency: 0.00001  dbSNP: rs762397298
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000217107 SCV000274621 uncertain significance Hereditary cancer-predisposing syndrome 2023-02-17 criteria provided, single submitter clinical testing The p.R90G variant (also known as c.268C>G), located in coding exon 2 of the CDKN2A (p14ARF) gene, results from a C to G substitution at nucleotide position 268. The arginine at codon 90 is replaced by glycine, an amino acid with dissimilar properties. This alteration was detected in a cohort of 308 childhood acute lymphoblastic leukemia cases (Li C et al. Pharmacogenet Genomics, 2022 Feb;32:43-50). This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV000699363 SCV000828069 uncertain significance Familial melanoma 2021-12-17 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 90 of the CDKN2A (p14ARF) protein (p.Arg90Gly). This variant is present in population databases (rs762397298, gnomAD 0.01%). This missense change has been observed in individual(s) with colorectal cancer (PMID: 28135145). ClinVar contains an entry for this variant (Variation ID: 230923). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Color Diagnostics, LLC DBA Color Health RCV000217107 SCV000906779 likely benign Hereditary cancer-predisposing syndrome 2016-09-06 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV003477725 SCV004221636 likely benign not provided 2022-11-17 criteria provided, single submitter clinical testing

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