ClinVar Miner

Submissions for variant NM_000075.4(CDK4):c.477del (p.Phe159fs) (rs786203016)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000166135 SCV000216907 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-20 criteria provided, single submitter clinical testing The c.477delT variant, located in coding exon 3 of the CDK4 gene, results from a deletion of one nucleotide at nucleotide position 477, causing a translational frameshift with a predicted alternate stop codon (p.F159Lfs*71). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. While alterations that result in premature stop codon are typically deleterious in nature for tumor suppressor genes, the CDK4 gene is a well described proto-oncogene and the cancer related phenotype is conventionally due to activating, or gain-of-function, mutations. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.
Invitae RCV000817621 SCV000958190 uncertain significance Hereditary melanoma 2018-11-05 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Phe159Leufs*71) in the CDK4 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with CDK4-related disease. ClinVar contains an entry for this variant (Variation ID: 186526). The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in CDK4 cause disease. 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.