Genetic Variant CDK5R2:p.Pro159Leu (chr2-218960296-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003936.5(CDK5R2):c.476C>T(p.Pro159Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000409 in 1,222,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

CDK5R2
NM_003936.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.26

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21997768).

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.476C>T	p.Pro159Leu	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.476C>T	p.Pro159Leu	missense	Exon 1 of 1	ENSP00000304250.4	Q13319
CDK5R2-AS1	ENST00000429343.1	TSL:4	n.45+1563G>A		intron	N/A
CDK5R2-AS1	ENST00000798770.1		n.277+1563G>A		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

26704

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000409

AC:

AN:

1222598

Hom.:

Cov.:

AF XY:

0.00000502

AC XY:

AN XY:

597352

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24006

American (AMR)

AF:

0.00

AC:

AN:

11044

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18318

East Asian (EAS)

AF:

0.000147

AC:

AN:

27294

South Asian (SAS)

AF:

0.00

AC:

AN:

53102

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3632

European-Non Finnish (NFE)

AF:

9.95e-7

AC:

AN:

1004880

Other (OTH)

AF:

0.00

AC:

AN:

49908

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.535

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.034

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.21

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.61

M_CAP

Pathogenic

0.55

MetaRNN

Benign

0.22

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.69

PhyloP100

2.3

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.10

REVEL

Benign

0.13

Sift

Benign

0.23

Sift4G

Benign

0.45

Polyphen

0.77

Vest4

0.25

MutPred

0.41

Loss of glycosylation at P159 (P = 3e-04)

MVP

0.64

ClinPred

0.27

GERP RS

2.0

Varity_R

0.069

gMVP

0.32

Mutation Taster

=96/4

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over