Genetic Variant CDK15:p.Arg247Gln (chr2-201835652-G-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001366386.2(CDK15):c.740G>A(p.Arg247Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000934 in 1,605,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000083 ( 0 hom. )

Consequence

CDK15
NM_001366386.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.83

Publications

0 publications found

Variant links:

Genes affected

CDK15 (HGNC:14434): (cyclin dependent kinase 15) Enables protein serine/threonine kinase activity. Predicted to be involved in protein phosphorylation and regulation of transcription involved in G1/S transition of mitotic cell cycle. Predicted to be active in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

CDK15 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.829

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366386.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDK15	NM_001366386.2	MANE Select	c.740G>A	p.Arg247Gln	missense	Exon 8 of 14	NP_001353315.1	Q96Q40-1
CDK15	NM_001261435.1		c.740G>A	p.Arg247Gln	missense	Exon 8 of 14	NP_001248364.1	Q96Q40-5
CDK15	NM_001261436.1		c.740G>A	p.Arg247Gln	missense	Exon 8 of 13	NP_001248365.1	Q96Q40-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDK15	ENST00000652192.3	MANE Select	c.740G>A	p.Arg247Gln	missense	Exon 8 of 14	ENSP00000498608.2	Q96Q40-1
CDK15	ENST00000450471.6	TSL:1	c.740G>A	p.Arg247Gln	missense	Exon 8 of 14	ENSP00000406472.2	Q96Q40-5
CDK15	ENST00000434439.1	TSL:1	c.740G>A	p.Arg247Gln	missense	Exon 8 of 13	ENSP00000412775.1	Q96Q40-3

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151740

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000727

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000279

AC:

AN:

251010

AF XY:

0.0000295

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000825

AC:

AN:

1454064

Hom.:

Cov.:

AF XY:

0.00000968

AC XY:

AN XY:

723512

show subpopulations

African (AFR)

AF:

0.0000599

AC:

AN:

33364

American (AMR)

AF:

0.00

AC:

AN:

44610

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25944

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39618

South Asian (SAS)

AF:

0.0000234

AC:

AN:

85404

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53088

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5190

European-Non Finnish (NFE)

AF:

0.00000632

AC:

AN:

1106950

Other (OTH)

AF:

0.00

AC:

AN:

59896

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

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:

0.0000198

AC:

AN:

151740

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

AN XY:

74072

show subpopulations

African (AFR)

AF:

0.0000727

AC:

AN:

41290

American (AMR)

AF:

0.00

AC:

AN:

15188

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10510

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67980

Other (OTH)

AF:

0.00

AC:

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

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:

0.0000386

Hom.:

Bravo

AF:

0.0000453

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000412

AC:

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

Pathogenic

0.84

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

0.13

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

Eigen

Pathogenic

0.71

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.046

MetaRNN

Pathogenic

0.83

MetaSVM

Uncertain

0.20

MutationAssessor

Uncertain

2.8

PhyloP100

6.8

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-3.9

REVEL

Uncertain

0.53

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Vest4

0.88

MVP

0.66

MPC

0.40

ClinPred

0.93

GERP RS

5.6

gMVP

0.57

Mutation Taster

=39/61

disease causing

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over