Variant chr9-120389821-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_018249.6(CDK5RAP2):c.5579-34G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.696 in 1,603,718 control chromosomes in the GnomAD database, including 389,918 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.71 ( 38705 hom., cov: 32)

Exomes 𝑓: 0.69 ( 351213 hom. )

Consequence

CDK5RAP2
NM_018249.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.832

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 9-120389821-C-G is Benign according to our data. Variant chr9-120389821-C-G is described in ClinVar as [Benign]. Clinvar id is 158168.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDK5RAP2	NM_018249.6 linkuse as main transcript	c.5579-34G>C		intron_variant		ENST00000349780.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDK5RAP2	ENST00000349780.9 linkuse as main transcript	c.5579-34G>C		intron_variant		1	NM_018249.6	P4	Q96SN8-1

Frequencies

GnomAD3 genomes

AF:

0.712

AC:

108190

AN:

152056

Hom.:

38664

Cov.:

show subpopulations

Gnomad AFR

AF:

0.733

Gnomad AMI

AF:

0.564

Gnomad AMR

AF:

0.749

Gnomad ASJ

AF:

0.648

Gnomad EAS

AF:

0.799

Gnomad SAS

AF:

0.670

Gnomad FIN

AF:

0.776

Gnomad MID

AF:

0.636

Gnomad NFE

AF:

0.682

Gnomad OTH

AF:

0.709

GnomAD3 exomes

AF:

0.717

AC:

179761

AN:

250576

Hom.:

64797

AF XY:

0.710

AC XY:

96126

AN XY:

135372

show subpopulations

Gnomad AFR exome

AF:

0.735

Gnomad AMR exome

AF:

0.794

Gnomad ASJ exome

AF:

0.657

Gnomad EAS exome

AF:

0.795

Gnomad SAS exome

AF:

0.670

Gnomad FIN exome

AF:

0.767

Gnomad NFE exome

AF:

0.688

Gnomad OTH exome

AF:

0.717

GnomAD4 exome

AF:

0.694

AC:

1007923

AN:

1451544

Hom.:

351213

Cov.:

AF XY:

0.693

AC XY:

500952

AN XY:

722778

show subpopulations

Gnomad4 AFR exome

AF:

0.735

Gnomad4 AMR exome

AF:

0.793

Gnomad4 ASJ exome

AF:

0.658

Gnomad4 EAS exome

AF:

0.786

Gnomad4 SAS exome

AF:

0.668

Gnomad4 FIN exome

AF:

0.768

Gnomad4 NFE exome

AF:

0.685

Gnomad4 OTH exome

AF:

0.693

GnomAD4 genome

AF:

0.712

AC:

108289

AN:

152174

Hom.:

38705

Cov.:

AF XY:

0.715

AC XY:

53188

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.733

Gnomad4 AMR

AF:

0.749

Gnomad4 ASJ

AF:

0.648

Gnomad4 EAS

AF:

0.799

Gnomad4 SAS

AF:

0.670

Gnomad4 FIN

AF:

0.776

Gnomad4 NFE

AF:

0.682

Gnomad4 OTH

AF:

0.709

Alfa

AF:

0.639

Hom.:

3966

Bravo

AF:

0.715

Asia WGS

AF:

0.770

AC:

2676

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Genetic Services Laboratory, University of Chicago

- -

Microcephaly 3, primary, autosomal recessive

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.25

DANN

Benign

0.44

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