Genetic Variant CDK13:p.Pro2Arg (chr7-39950646-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_003718.5(CDK13):c.5C>G(p.Pro2Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000127 in 1,333,646 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P2L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

CDK13
NM_003718.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.49

Publications

0 publications found

Variant links:

Genes affected

CDK13 (HGNC:1733): (cyclin dependent kinase 13) The protein encoded by this gene is a member of the cyclin-dependent serine/threonine protein kinase family. Members of this family are well known for their essential roles as master switches in cell cycle control. The exact function of this protein has not yet been determined, but it may play a role in mRNA processing and may be involved in regulation of hematopoiesis. Alternatively spliced transcript variants have been described.[provided by RefSeq, Dec 2009]

CDK13 Gene-Disease associations (from GenCC):

congenital heart defects, dysmorphic facial features, and intellectual developmental disorder
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Illumina
syndromic intellectual disability
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

CDK13 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAdExome4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK13	NM_003718.5 link	c.5C>G	p.Pro2Arg	missense_variant	Exon 1 of 14	ENST00000181839.10	NP_003709.3	Q14004-1A0A024RA85Q9BVE2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK13	ENST00000181839.10 link	c.5C>G	p.Pro2Arg	missense_variant	Exon 1 of 14	1	NM_003718.5	ENSP00000181839.4		Q14004-1
CDK13	ENST00000340829.10 link	c.5C>G	p.Pro2Arg	missense_variant	Exon 1 of 14	1		ENSP00000340557.5		Q14004-2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152142

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000118

AC:

AN:

1181504

Hom.:

Cov.:

AF XY:

0.0000158

AC XY:

AN XY:

570096

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23656

American (AMR)

AF:

0.000102

AC:

AN:

9844

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16462

East Asian (EAS)

AF:

0.0000371

AC:

AN:

26918

South Asian (SAS)

AF:

0.00

AC:

AN:

47974

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28310

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3284

European-Non Finnish (NFE)

AF:

0.0000123

AC:

AN:

976832

Other (OTH)

AF:

0.00

AC:

AN:

48224

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152142

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41432

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68012

Other (OTH)

AF:

0.00

AC:

AN:

2088

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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000227

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Uncertain

0.074

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.11

T;.

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.61

T;T

M_CAP

Pathogenic

0.87

MetaRNN

Uncertain

0.65

D;D

MetaSVM

Benign

-0.76

PhyloP100

1.5

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-0.89

N;N

REVEL

Uncertain

0.42

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.64

P;P

Vest4

0.47

MutPred

0.18

Gain of MoRF binding (P = 0.0039);Gain of MoRF binding (P = 0.0039);

MVP

0.64

MPC

1.8

ClinPred

0.60

GERP RS

2.8

PromoterAI

-0.062

Neutral

(source)

Varity_R

0.20

gMVP

0.46

Mutation Taster

=88/12

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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7-39950646-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over