ClinVar Miner

Submissions for variant NM_000075.4(CDK4):c.184C>T (p.Arg62Ter)

gnomAD frequency: 0.00001  dbSNP: rs745481376
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 RCV001013378 SCV001173957 uncertain significance Hereditary cancer-predisposing syndrome 2022-10-27 criteria provided, single submitter clinical testing The p.R62* variant (also known as c.184C>T), located in coding exon 1 of the CDK4 gene, results from a C to T substitution at nucleotide position 184. This changes the amino acid from an arginine to a stop codon within coding exon 1. This alteration has been reported as a somatic finding in breast cancer (Huang KL et al. Cell, 2018 04;173:355-370.e14). This alteration has also been reported as a germline finding in a colorectal cancer patient (Gong R et al. Cancer Manag Res, 2019 Apr;11:3721-3739). 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.
Invitae RCV003746575 SCV004507423 uncertain significance Familial melanoma 2023-02-04 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg62*) 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 present in population databases (rs745481376, gnomAD 0.007%). 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: 820176). 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.

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.