rs34523498

Positions:

chr9-120443703-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018249.6(CDK5RAP2):c.3065G>A(p.Gly1022Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0275 in 1,614,004 control chromosomes in the GnomAD database, including 704 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 80 hom., cov: 33)

Exomes 𝑓: 0.027 ( 624 hom. )

Consequence

CDK5RAP2
NM_018249.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7O:1

Conservation

PhyloP100: 0.567

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:

CDK5RAP2 (HGNC:):

CDK5RAP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001809448).

BP6

Variant 9-120443703-C-T is Benign according to our data. Variant chr9-120443703-C-T is described in ClinVar as [Benign]. Clinvar id is 21645.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-120443703-C-T is described in Lovd as [Benign].

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDK5RAP2	NM_018249.6 linkuse as main transcript	c.3065G>A	p.Gly1022Glu	missense_variant	23/38	ENST00000349780.9	NP_060719.4	Q96SN8-1B3KVI2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDK5RAP2	ENST00000349780.9 linkuse as main transcript	c.3065G>A	p.Gly1022Glu	missense_variant	23/38	1	NM_018249.6	ENSP00000343818.4		Q96SN8-1

Frequencies

GnomAD3 genomes

AF:

0.0290

AC:

4408

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0338

Gnomad AMI

AF:

0.125

Gnomad AMR

AF:

0.0160

Gnomad ASJ

AF:

0.0161

Gnomad EAS

AF:

0.0408

Gnomad SAS

AF:

0.00602

Gnomad FIN

AF:

0.0413

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0273

Gnomad OTH

AF:

0.0206

GnomAD3 exomes

AF:

0.0250

AC:

6273

AN:

251176

Hom.:

112

AF XY:

0.0240

AC XY:

3260

AN XY:

135722

show subpopulations

Gnomad AFR exome

AF:

0.0344

Gnomad AMR exome

AF:

0.0135

Gnomad ASJ exome

AF:

0.0144

Gnomad EAS exome

AF:

0.0378

Gnomad SAS exome

AF:

0.00683

Gnomad FIN exome

AF:

0.0383

Gnomad NFE exome

AF:

0.0282

Gnomad OTH exome

AF:

0.0280

GnomAD4 exome

AF:

0.0273

AC:

39917

AN:

1461750

Hom.:

624

Cov.:

AF XY:

0.0266

AC XY:

19328

AN XY:

727176

show subpopulations

Gnomad4 AFR exome

AF:

0.0331

Gnomad4 AMR exome

AF:

0.0135

Gnomad4 ASJ exome

AF:

0.0149

Gnomad4 EAS exome

AF:

0.0680

Gnomad4 SAS exome

AF:

0.00710

Gnomad4 FIN exome

AF:

0.0359

Gnomad4 NFE exome

AF:

0.0276

Gnomad4 OTH exome

AF:

0.0268

GnomAD4 genome

AF:

0.0290

AC:

4418

AN:

152254

Hom.:

Cov.:

AF XY:

0.0293

AC XY:

2184

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0339

Gnomad4 AMR

AF:

0.0160

Gnomad4 ASJ

AF:

0.0161

Gnomad4 EAS

AF:

0.0409

Gnomad4 SAS

AF:

0.00540

Gnomad4 FIN

AF:

0.0413

Gnomad4 NFE

AF:

0.0273

Gnomad4 OTH

AF:

0.0232

Alfa

AF:

0.0283

Hom.:

121

Bravo

AF:

0.0287

TwinsUK

AF:

0.0264

AC:

ALSPAC

AF:

0.0257

AC:

ESP6500AA

AF:

0.0361

AC:

159

ESP6500EA

AF:

0.0290

AC:

249

ExAC

AF:

0.0263

AC:

3191

Asia WGS

AF:

0.0400

AC:

139

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Microcephaly 3, primary, autosomal recessive

Other:1

not provided, no classification provided

literature only

GeneReviews

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

.;T;.;.

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.73

T;T;T;T

MetaRNN

Benign

0.0018

T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.4

.;L;L;.

PrimateAI

Benign

0.31

PROVEAN

Benign

-2.2

.;N;N;N

REVEL

Benign

0.027

Sift

Uncertain

0.024

.;D;D;D

Sift4G

Benign

0.40

T;T;T;T

Polyphen

0.053, 0.24, 1.0

.;B;B;D

Vest4

0.15

MPC

0.48

ClinPred

0.0062

GERP RS

0.51

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.086

gMVP

0.10

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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