Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001244623 | SCV001417856 | uncertain significance | Familial melanoma | 2024-04-10 | criteria provided, single submitter | clinical testing | The CDKN2A gene encodes two different proteins, p16INK4a and p14ARF, which are translated from alternative transcripts with different open reading frames. Both transcripts have been analyzed. We report either the variant with the higher classification or default to the CDKN2A (p16INK4a) variant. This report therefore includes the details for the CDKN2A (p16INK4a) variant. This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 62 of the CDKN2A (p16INK4a) protein (p.Leu62Val). 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. This variant is also known as c.227C>G (p.Ala76Gly) in the CDKN2A (p14ARF) transcript. ClinVar contains an entry for this variant (Variation ID: 969307). 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. 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. |
Ambry Genetics | RCV003166534 | SCV003860806 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-01-12 | criteria provided, single submitter | clinical testing | The p.L62V variant (also known as c.184C>G), located in coding exon 2 of the CDKN2A gene, results from a C to G substitution at nucleotide position 184. The leucine at codon 62 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |