ClinVar Miner

Submissions for variant NM_000075.4(CDK4):c.523-4T>A (rs587780667)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001085786 SCV000166200 likely benign Hereditary melanoma 2020-11-23 criteria provided, single submitter clinical testing
Ambry Genetics RCV000564591 SCV000669085 uncertain significance Hereditary cancer-predisposing syndrome 2019-08-29 criteria provided, single submitter clinical testing The c.523-4T>A intronic variant results from a T to A substitution 4 nucleotides upstream from 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 acceptor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000589608 SCV000695319 benign not provided 2017-05-08 criteria provided, single submitter clinical testing Variant summary: The CDK4 c.523-4T>A variant involves the alteration of a non-conserved intronic nucleotide and 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 10/121352 control chromosomes, predominantly observed in the South Asian subpopulation at a frequency of 0.000545 (9/16512). This frequency is about 27 times the estimated maximal expected allele frequency of a pathogenic CDK4 variant (0.00002), suggesting this is likely a benign polymorphism found primarily in the populations of South Asian origin. In addition, a clinical diagnostic laboratory classified this variant as likely benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign.

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