dbSNP rs1370035953: CDK5R2:p.Asp110Glu (chr2-218960150-T-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003936.5(CDK5R2):c.330T>A(p.Asp110Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000448 in 1,561,728 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: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

CDK5R2
NM_003936.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00100

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.049374163).

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.330T>A	p.Asp110Glu	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.330T>A	p.Asp110Glu	missense	Exon 1 of 1	ENSP00000304250.4	Q13319
CDK5R2-AS1	ENST00000429343.1	TSL:4	n.45+1709A>T		intron	N/A
CDK5R2-AS1	ENST00000798770.1		n.277+1709A>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00000661

AC:

AN:

151252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000425

AC:

AN:

1410476

Hom.:

Cov.:

AF XY:

0.00000571

AC XY:

AN XY:

700166

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29724

American (AMR)

AF:

0.00

AC:

AN:

38402

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24924

East Asian (EAS)

AF:

0.00

AC:

AN:

34344

South Asian (SAS)

AF:

0.00

AC:

AN:

80830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47156

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5510

European-Non Finnish (NFE)

AF:

0.00000458

AC:

AN:

1091176

Other (OTH)

AF:

0.0000171

AC:

AN:

58410

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000661

AC:

AN:

151252

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73822

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41232

American (AMR)

AF:

0.00

AC:

AN:

15216

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3458

East Asian (EAS)

AF:

0.00

AC:

AN:

5128

South Asian (SAS)

AF:

0.00

AC:

AN:

4806

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10364

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67742

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

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

0.084

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.069

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.43

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.049

MetaSVM

Benign

-0.87

MutationAssessor

Benign

0.55

PhyloP100

0.0010

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

0.14

REVEL

Benign

0.20

Sift

Benign

0.95

Sift4G

Benign

0.98

Polyphen

0.0

Vest4

0.057

MutPred

0.56

Gain of methylation at K107 (P = 0.1175)

MVP

0.28

ClinPred

0.087

GERP RS

-7.9

PromoterAI

-0.032

Neutral

(source)

Varity_R

0.031

gMVP

0.18

Mutation Taster

=95/5

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