Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV003354439 | SCV004073711 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-07-24 | criteria provided, single submitter | clinical testing | The c.694_706dup13 variant, located in coding exon 6 of the CDK4 gene, results from a duplication of 13 nucleotides (CTGCCTCCAGAGG) at nucleotide positions 694 to 706, causing a translational frameshift with a predicted alternate stop codon (p.D236Afs*6). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in protein truncation or nonsense-mediated mRNA decay. However, loss of function of CDK4 has not been established as a mechanism of disease. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV005104123 | SCV005807652 | uncertain significance | Familial melanoma | 2024-07-03 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Asp236Alafs*6) in the CDK4 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in CDK4 cause disease. This variant is not present in population databases (gnomAD no frequency). 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: 2603199). 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. |