Submissions for variant NM_018249.6(CDK5RAP2):c.923C>T (p.Thr308Ile)

gnomAD frequency: 0.00023  dbSNP: rs145272328

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000145510	SCV000192598	uncertain significance	Microcephaly 3, primary, autosomal recessive	2014-03-19	criteria provided, single submitter	clinical testing
GeneDx	RCV000487957	SCV000567990	uncertain significance	not provided	2015-10-06	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the CDK5RAP2 gene. The T308I variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The T308I variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
CeGaT Center for Human Genetics Tuebingen	RCV000487957	SCV000575590	likely benign	not provided	2023-07-01	criteria provided, single submitter	clinical testing	CDK5RAP2: BP4
Invitae	RCV000487957	SCV001070186	likely benign	not provided	2024-01-18	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000145510	SCV001329503	uncertain significance	Microcephaly 3, primary, autosomal recessive	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
PreventionGenetics, part of Exact Sciences	RCV003945165	SCV004759922	likely benign	CDK5RAP2-related disorder	2020-03-10	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).