ClinVar Miner

Submissions for variant NM_000077.5(CDKN2A):c.418A>C (p.Ser140Arg)

dbSNP: rs1587330504
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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 RCV001022008 SCV001183695 uncertain significance Hereditary cancer-predisposing syndrome 2021-06-28 criteria provided, single submitter clinical testing The p.S140R variant (also known as c.418A>C), located in coding exon 2 of the CDKN2A gene, results from an A to C substitution at nucleotide position 418. The serine at codon 140 is replaced by arginine, an amino acid with dissimilar properties. 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.
Color Diagnostics, LLC DBA Color Health RCV001022008 SCV001353031 uncertain significance Hereditary cancer-predisposing syndrome 2019-01-03 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001319139 SCV001509870 uncertain significance Familial melanoma 2024-09-15 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 140 of the CDKN2A (p16INK4a) protein (p.Ser140Arg). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CDKN2A (p16INK4a)-related conditions. ClinVar contains an entry for this variant (Variation ID: 824656). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on CDKN2A (p16INK4a) function (PMID: 8573142). 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.
GeneDx RCV002305560 SCV002599719 uncertain significance not provided 2022-11-04 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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