ClinVar Miner

Submissions for variant NM_018249.6(CDK5RAP2):c.524_528del (p.Gln175fs)

gnomAD frequency: 0.00004  dbSNP: rs587783393
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000115025 SCV000192580 pathogenic Microcephaly 3, primary, autosomal recessive 2013-08-15 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000115025 SCV000916246 uncertain significance Microcephaly 3, primary, autosomal recessive 2017-09-25 criteria provided, single submitter clinical testing The CDK5RAP2 c.524_528delAGGCA (p.Gln175ArgfsTer42) variant results in a frameshift, and is predicted to result in premature termination of the protein. The p.Gln175ArgfsTer42 variant has been reported in one study in which it was found in a compound heterozygous state with variant affecting a splice acceptor site in a six-year old girl with primary autosomal recessive microcephaly (Tan et al. 2014). The patient was one of triplets and is reported to have severe microcephaly and developmental delay. Her two siblings were unaffected and were not tested for the variant. The p.Gln175ArgfsTer42 variant was also detected in a heterozygous state in the unaffected father. Control data are unavailable for this variant, which is reported at a frequency of 0.000125 in the African population of the Genome Aggregation Database. Due to the potential impact of frameshift variants but limited evidence, the p.Gln175ArgfsTer42 variant is classified as a variant unknown significance but suspicious for pathogenicity for the recessive form of primary microcephaly. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV002515791 SCV003302602 pathogenic not provided 2023-07-25 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 127196). This premature translational stop signal has been observed in individual(s) with Seckel Syndrome (PMID: 23726037). This variant is present in population databases (rs587783393, gnomAD 0.01%). This sequence change creates a premature translational stop signal (p.Gln175Argfs*42) in the CDK5RAP2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CDK5RAP2 are known to be pathogenic (PMID: 15793586, 20460369, 26436113).
OMIM RCV000115025 SCV000148934 pathogenic Microcephaly 3, primary, autosomal recessive 2014-04-01 no assertion criteria provided literature only

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.