Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000568233 | SCV000669123 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-06-15 | criteria provided, single submitter | clinical testing | The c.355-4C>G intronic variant results from a C to G substitution 4 nucleotides upstream from coding exon 3 in the CDK4 gene. This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will result in the creation or strengthening of a novel splice acceptor site. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV003746543 | SCV004523563 | uncertain significance | Familial melanoma | 2023-11-29 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 3 of the CDK4 gene. It does not directly change the encoded amino acid sequence of the CDK4 protein. This variant is present in population databases (no rsID available, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with CDK4-related conditions. ClinVar contains an entry for this variant (Variation ID: 483294). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |