Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001242276 | SCV001415350 | uncertain significance | Familial melanoma | 2019-06-26 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with CDKN2A (p16INK4a)-related conditions. The p.Trp110Arg variant has been reported not to substantially affect CDKN2A (p16INK4a) protein function (PMID: 12606942). The functional impact of p.Leu124Gln on p14ARF has not been tested. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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. The CDKN2A gene encodes two different proteins, p16INK4a and p14ARF, which are translated from alternative transcripts that have different open reading frames. This sequence change replaces tryptophan with arginine at codon 110 of the CDKN2A (p16INK4a) protein (p.Trp110Arg). The tryptophan residue is highly conserved and there is a moderate physicochemical difference between tryptophan and arginine. Alternatively, this sequence change replaces leucine with glutamine at codon 124 of the CDKN2A (p14ARF) protein (p.Leu124Gln). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and glutamine. |