Genetic Variant CDK5R2:p.Gly149Asp (chr2-218960266-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_003936.5(CDK5R2):c.446G>A(p.Gly149Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G149S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CDK5R2
NM_003936.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.720

Publications

0 publications found

Variant links:

Genes affected

CDK5R2 (HGNC:1776): (cyclin dependent kinase 5 regulatory subunit 2) The protein encoded by this gene is a neuron-specific activator of CDK5 kinase. It associates with CDK5 to form an active kinase. This protein and neuron-specific CDK5 activator CDK5R1/p39NCK5A both share limited similarity to cyclins, and thus may define a distinct family of cyclin-dependent kinase activating proteins. [provided by RefSeq, Jul 2008]

CDK5R2 links:

CDK5R2-AS1 (HGNC:55677): (CDK5R2 antisense RNA 1)

CDK5R2-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29588103).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003936.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK5R2	NM_003936.5	MANE Select	c.446G>A	p.Gly149Asp	missense	Exon 1 of 1	NP_003927.1	Q13319

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDK5R2	ENST00000302625.6	TSL:6 MANE Select	c.446G>A	p.Gly149Asp	missense	Exon 1 of 1	ENSP00000304250.4	Q13319
CDK5R2-AS1	ENST00000429343.1	TSL:4	n.45+1593C>T		intron	N/A
CDK5R2-AS1	ENST00000798770.1		n.277+1593C>T		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1125852

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

540582

African (AFR)

AF:

0.00

AC:

AN:

22668

American (AMR)

AF:

0.00

AC:

AN:

8334

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14416

East Asian (EAS)

AF:

0.00

AC:

AN:

25890

South Asian (SAS)

AF:

0.00

AC:

AN:

29180

European-Finnish (FIN)

AF:

0.00

AC:

AN:

24944

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3110

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

952022

Other (OTH)

AF:

0.00

AC:

AN:

45288

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.028

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.089

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.48

M_CAP

Pathogenic

0.81

MetaRNN

Benign

0.30

MetaSVM

Benign

-0.76

MutationAssessor

Benign

1.0

PhyloP100

0.72

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-0.66

REVEL

Benign

0.22

Sift

Benign

0.16

Sift4G

Benign

0.37

Polyphen

0.96

Vest4

0.081

MutPred

0.34

Gain of solvent accessibility (P = 0.0638)

MVP

0.70

ClinPred

0.40

GERP RS

2.8

Varity_R

0.15

gMVP

0.33

Mutation Taster

=98/2

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over