ClinVar Miner

Submissions for variant NM_018249.6(CDK5RAP2):c.4338T>A (p.Ser1446Arg)

gnomAD frequency: 0.00009  dbSNP: rs143341041
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000145483 SCV000192568 uncertain significance Microcephaly 3, primary, autosomal recessive 2013-02-08 criteria provided, single submitter clinical testing
GeneDx RCV000658288 SCV000780059 uncertain significance not provided 2018-05-17 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the CDK5RAP2 gene. The S1446R variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The S1446R variant is observed in 185/34420 (0.5%) alleles from individuals of Latino background in large population cohorts, which is greater than expected for this disorder. (Lek et al., 2016). However, the S1446R variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000658288 SCV001022602 likely benign not provided 2023-11-07 criteria provided, single submitter clinical testing
Baylor Genetics RCV000145483 SCV001529817 uncertain significance Microcephaly 3, primary, autosomal recessive 2018-01-26 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
PreventionGenetics, part of Exact Sciences RCV003975143 SCV004788184 likely benign CDK5RAP2-related condition 2020-04-24 criteria provided, single submitter clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

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