rs2501727

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_018249.6(CDK5RAP2):c.2274T>C(p.Asp758Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 1,613,736 control chromosomes in the GnomAD database, including 16,296 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3729 hom., cov: 32)

Exomes 𝑓: 0.12 ( 12567 hom. )

Consequence

CDK5RAP2
NM_018249.6 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.311

Variant links:

Genes affected

CDK5RAP2 (HGNC:18672): (CDK5 regulatory subunit associated protein 2) This gene encodes a regulator of CDK5 (cyclin-dependent kinase 5) activity. The protein encoded by this gene is localized to the centrosome and Golgi complex, interacts with CDK5R1 and pericentrin (PCNT), plays a role in centriole engagement and microtubule nucleation, and has been linked to primary microcephaly and Alzheimer's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2013]

CDK5RAP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 9-120458551-A-G is Benign according to our data. Variant chr9-120458551-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 136705.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-120458551-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.311 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK5RAP2	NM_018249.6 link	c.2274T>C	p.Asp758Asp	synonymous_variant	Exon 20 of 38	ENST00000349780.9	NP_060719.4	Q96SN8-1B3KVI2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK5RAP2	ENST00000349780.9 link	c.2274T>C	p.Asp758Asp	synonymous_variant	Exon 20 of 38	1	NM_018249.6	ENSP00000343818.4		Q96SN8-1

Frequencies

GnomAD3 genomes

AF:

0.186

AC:

28339

AN:

151978

Hom.:

3708

Cov.:

show subpopulations

Gnomad AFR

AF:

0.355

Gnomad AMI

AF:

0.171

Gnomad AMR

AF:

0.165

Gnomad ASJ

AF:

0.0856

Gnomad EAS

AF:

0.330

Gnomad SAS

AF:

0.147

Gnomad FIN

AF:

0.118

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.0980

Gnomad OTH

AF:

0.160

GnomAD3 exomes

AF:

0.147

AC:

36956

AN:

251390

Hom.:

3635

AF XY:

0.141

AC XY:

19105

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.365

Gnomad AMR exome

AF:

0.153

Gnomad ASJ exome

AF:

0.0883

Gnomad EAS exome

AF:

0.319

Gnomad SAS exome

AF:

0.138

Gnomad FIN exome

AF:

0.109

Gnomad NFE exome

AF:

0.102

Gnomad OTH exome

AF:

0.125

GnomAD4 exome

AF:

0.115

AC:

168786

AN:

1461640

Hom.:

12567

Cov.:

AF XY:

0.115

AC XY:

83606

AN XY:

727134

show subpopulations

Gnomad4 AFR exome

AF:

0.359

Gnomad4 AMR exome

AF:

0.155

Gnomad4 ASJ exome

AF:

0.0837

Gnomad4 EAS exome

AF:

0.353

Gnomad4 SAS exome

AF:

0.137

Gnomad4 FIN exome

AF:

0.109

Gnomad4 NFE exome

AF:

0.0963

Gnomad4 OTH exome

AF:

0.136

GnomAD4 genome

AF:

0.187

AC:

28408

AN:

152096

Hom.:

3729

Cov.:

AF XY:

0.188

AC XY:

13972

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.355

Gnomad4 AMR

AF:

0.164

Gnomad4 ASJ

AF:

0.0856

Gnomad4 EAS

AF:

0.330

Gnomad4 SAS

AF:

0.146

Gnomad4 FIN

AF:

0.118

Gnomad4 NFE

AF:

0.0980

Gnomad4 OTH

AF:

0.164

Alfa

AF:

0.119

Hom.:

2396

Bravo

AF:

0.198

Asia WGS

AF:

0.292

AC:

1018

AN:

3478

EpiCase

AF:

0.0983

EpiControl

AF:

0.101

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 18, 2013

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Microcephaly 3, primary, autosomal recessive

Benign:2

Jun 28, 2017

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Primary Microcephaly, Recessive

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.90

DANN

Benign

0.27

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over