Submissions for variant NM_018249.6(CDK5RAP2):c.2003A>G (p.Tyr668Cys)

gnomAD frequency: 0.00029  dbSNP: rs137966123

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000194516	SCV000246927	uncertain significance	not specified	2015-07-31	criteria provided, single submitter	clinical testing
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000194516	SCV000258130	uncertain significance	not specified	2015-06-11	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001007670	SCV000476943	uncertain significance	Microcephaly 3, primary, autosomal recessive	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae	RCV000885604	SCV001029063	likely benign	not provided	2024-01-30	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000885604	SCV001501041	likely benign	not provided	2023-11-01	criteria provided, single submitter	clinical testing	CDK5RAP2: BP4
GeneDx	RCV000885604	SCV003853183	uncertain significance	not provided	2022-10-03	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31696992)
PreventionGenetics, part of Exact Sciences	RCV003947601	SCV004761526	likely benign	CDK5RAP2-related disorder	2022-09-30	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).
Ambry Genetics	RCV004020312	SCV004922130	uncertain significance	Inborn genetic diseases	2021-05-16	criteria provided, single submitter	clinical testing	The c.2003A>G (p.Y668C) alteration is located in exon 18 (coding exon 18) of the CDK5RAP2 gene. This alteration results from a A to G substitution at nucleotide position 2003, causing the tyrosine (Y) at amino acid position 668 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Institut de Recherche Interdisciplinaire en Biologie Humaine et Moleculaire, Universite Libre de Bruxelles	RCV001007670	SCV000998538	uncertain significance	Microcephaly 3, primary, autosomal recessive		no assertion criteria provided	clinical testing