Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001025137 | SCV001187269 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-08-04 | criteria provided, single submitter | clinical testing | The c.632+4T>A intronic variant results from a T to A substitution 4 nucleotides after coding exon 4 in the CDK4 gene. This nucleotide position is not well conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is not predicted to have any significant effect on this splice donor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Labcorp Genetics |
RCV002551917 | SCV003335462 | uncertain significance | Familial melanoma | 2023-10-05 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 5 of the CDK4 gene. It does not directly change the encoded amino acid sequence of the CDK4 protein. It affects a nucleotide within the consensus splice site. 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: 826324). Variants that disrupt 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 is not likely to affect RNA splicing. 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. |
Myriad Genetics, |
RCV004789360 | SCV005405658 | likely benign | Melanoma, cutaneous malignant, susceptibility to, 3 | 2024-09-26 | criteria provided, single submitter | clinical testing | This variant is considered likely benign. This variant is intronic and is not expected to impact mRNA splicing. |