Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002342138 | SCV002636068 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-10-08 | criteria provided, single submitter | clinical testing | The c.457+5G>T intronic variant results from a G to T substitution 5 nucleotides after coding exon 2 in the CDKN2A gene. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003585257 | SCV004270680 | uncertain significance | Familial melanoma | 2020-03-10 | criteria provided, single submitter | clinical testing | 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. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with CDKN2A (p16INK4a)-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change falls in intron 2 of the CDKN2A (p16INK4a) gene. It does not directly change the encoded amino acid sequence of the CDKN2A (p16INK4a) protein, but it affects a nucleotide within the consensus splice site of the intron. |