Genetic Variant CDK20:p.Ala295Thr (chr9-87967620-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_001039803.3(CDK20):c.883G>A(p.Ala295Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000253 in 1,504,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

CDK20
NM_001039803.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.48

Publications

0 publications found

Variant links:

Genes affected

CDK20 (HGNC:21420): (cyclin dependent kinase 20) The protein encoded by this gene contains a kinase domain most closely related to the cyclin-dependent protein kinases. The encoded kinase may activate cyclin-dependent kinase 2 and is involved in cell growth. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Dec 2009]

CDK20 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

CDK20 links:

ENSG00000303948 (HGNC:):

ENSG00000303948 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=0.1847235).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039803.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDK20	NM_001039803.3	MANE Select	c.883G>A	p.Ala295Thr	missense	Exon 8 of 8	NP_001034892.1	Q8IZL9-1
CDK20	NM_178432.4		c.859G>A	p.Ala287Thr	missense	Exon 7 of 7	NP_848519.1	Q8IZL9-4
CDK20	NM_012119.5		c.820G>A	p.Ala274Thr	missense	Exon 7 of 7	NP_036251.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDK20	ENST00000325303.9	TSL:1 MANE Select	c.883G>A	p.Ala295Thr	missense	Exon 8 of 8	ENSP00000322343.8	Q8IZL9-1
CDK20	ENST00000375883.7	TSL:1	c.820G>A	p.Ala274Thr	missense	Exon 7 of 7	ENSP00000365043.3	Q8IZL9-5
CDK20	ENST00000605159.5	TSL:1	c.792G>A	p.Leu264Leu	synonymous	Exon 7 of 7	ENSP00000474485.1	Q8IZL9-3

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000836

AC:

AN:

119604

AF XY:

0.00

show subpopulations

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:

0.0000218

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000244

AC:

AN:

1352548

Hom.:

Cov.:

AF XY:

0.0000333

AC XY:

AN XY:

660784

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30538

American (AMR)

AF:

0.00

AC:

AN:

30904

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21808

East Asian (EAS)

AF:

0.00

AC:

AN:

35284

South Asian (SAS)

AF:

0.00

AC:

AN:

71136

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47374

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5460

European-Non Finnish (NFE)

AF:

0.0000304

AC:

AN:

1054100

Other (OTH)

AF:

0.0000179

AC:

AN:

55944

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

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

AF:

0.0000329

AC:

AN:

152164

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41442

American (AMR)

AF:

0.0000654

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000869

Hom.:

Bravo

AF:

0.0000227

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

0.13

BayesDel_addAF

Benign

0.0057

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.014

Eigen

Benign

0.11

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.082

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.79

PhyloP100

5.5

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-1.0

REVEL

Benign

0.071

Sift

Benign

0.099

Sift4G

Benign

0.27

Polyphen

0.011

Vest4

0.24

MutPred

0.24

Gain of glycosylation at A295 (P = 0.0014)

MVP

0.56

MPC

0.037

ClinPred

0.98

GERP RS

4.7

Varity_R

0.18

gMVP

0.27

Mutation Taster

=76/24

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over