Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001338116 | SCV001531756 | uncertain significance | Familial melanoma | 2024-02-15 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg252Glnfs*12) in the CDK4 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 52 amino acid(s) of the CDK4 protein. This variant is present in population databases (rs754187815, gnomAD 0.002%). 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: 1035270). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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 | RCV002395737 | SCV002670783 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-09-13 | criteria provided, single submitter | clinical testing | The c.753dupC variant, located in coding exon 6 of the CDK4 gene, results from a duplication of C at nucleotide position 753, causing a translational frameshift with a predicted alternate stop codon (p.R252Qfs*12). This alteration occurs at the 3' terminus of theCDK4 gene, is not expected to trigger nonsense-mediated mRNAdecay and only impacts the last 40 amino acids of the protein. In addition, loss of function of CDK4 has not been clearly established as a mechanism of disease. Based on the available evidence, the clinical significance of this variant remains unclear. |