rs75029577

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_018249.6(CDK5RAP2):c.1093-14G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0277 in 1,608,532 control chromosomes in the GnomAD database, including 733 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 57 hom., cov: 29)

Exomes 𝑓: 0.028 ( 676 hom. )

Consequence

CDK5RAP2
NM_018249.6 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.0770

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 9-120518659-C-T is Benign according to our data. Variant chr9-120518659-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 136708.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-120518659-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0214 (3245/151878) while in subpopulation NFE AF= 0.0291 (1975/67946). AF 95% confidence interval is 0.028. There are 57 homozygotes in gnomad4. There are 1686 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 57 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK5RAP2	NM_018249.6 link	c.1093-14G>A		intron_variant	Intron 11 of 37	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.1093-14G>A		intron_variant	Intron 11 of 37	1	NM_018249.6	ENSP00000343818.4		Q96SN8-1

Frequencies

GnomAD3 genomes

AF:

0.0214

AC:

3243

AN:

151760

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00506

Gnomad AMI

AF:

0.0504

Gnomad AMR

AF:

0.0121

Gnomad ASJ

AF:

0.00807

Gnomad EAS

AF:

0.000579

Gnomad SAS

AF:

0.0261

Gnomad FIN

AF:

0.0606

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0291

Gnomad OTH

AF:

0.0144

GnomAD3 exomes

AF:

0.0238

AC:

5972

AN:

251054

Hom.:

AF XY:

0.0246

AC XY:

3342

AN XY:

135682

show subpopulations

Gnomad AFR exome

AF:

0.00381

Gnomad AMR exome

AF:

0.00760

Gnomad ASJ exome

AF:

0.00814

Gnomad EAS exome

AF:

0.000326

Gnomad SAS exome

AF:

0.0276

Gnomad FIN exome

AF:

0.0578

Gnomad NFE exome

AF:

0.0294

Gnomad OTH exome

AF:

0.0210

GnomAD4 exome

AF:

0.0284

AC:

41338

AN:

1456654

Hom.:

676

Cov.:

AF XY:

0.0286

AC XY:

20733

AN XY:

725094

show subpopulations

Gnomad4 AFR exome

AF:

0.00374

Gnomad4 AMR exome

AF:

0.00749

Gnomad4 ASJ exome

AF:

0.00808

Gnomad4 EAS exome

AF:

0.000227

Gnomad4 SAS exome

AF:

0.0288

Gnomad4 FIN exome

AF:

0.0557

Gnomad4 NFE exome

AF:

0.0304

Gnomad4 OTH exome

AF:

0.0246

GnomAD4 genome

AF:

0.0214

AC:

3245

AN:

151878

Hom.:

Cov.:

AF XY:

0.0227

AC XY:

1686

AN XY:

74230

show subpopulations

Gnomad4 AFR

AF:

0.00505

Gnomad4 AMR

AF:

0.0121

Gnomad4 ASJ

AF:

0.00807

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.0263

Gnomad4 FIN

AF:

0.0606

Gnomad4 NFE

AF:

0.0291

Gnomad4 OTH

AF:

0.0143

Alfa

AF:

0.0235

Hom.:

Bravo

AF:

0.0167

Asia WGS

AF:

0.0100

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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. -

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

-0.83

CADD

Benign

1.5

DANN

Benign

0.70

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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