Genetic Variant CDK13:p.Pro2Gln (chr7-39950646-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003718.5(CDK13):c.5C>A(p.Pro2Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000846 in 1,181,504 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: not found (cov: 32)

Exomes 𝑓: 8.5e-7 ( 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK13	NM_003718.5 link	c.5C>A	p.Pro2Gln	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>A	p.Pro2Gln	missense_variant	Exon 1 of 14	1	NM_003718.5	ENSP00000181839.4		Q14004-1
CDK13	ENST00000340829.10 link	c.5C>A	p.Pro2Gln	missense_variant	Exon 1 of 14	1		ENSP00000340557.5		Q14004-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

6646

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:

8.46e-7

AC:

AN:

1181504

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

570096

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23656

American (AMR)

AF:

0.00

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:

0.00

AC:

AN:

976832

Other (OTH)

AF:

0.00

AC:

AN:

48224

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

GnomAD4 genome

Cov.:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.34

BayesDel_addAF

Uncertain

0.062

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.11

T;.

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.59

T;T

M_CAP

Pathogenic

0.78

MetaRNN

Uncertain

0.44

T;T

MetaSVM

Benign

-0.89

PhyloP100

1.5

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.90

N;N

REVEL

Uncertain

0.33

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.065

B;B

Vest4

0.38

MutPred

0.12

Loss of catalytic residue at P2 (P = 0.0095);Loss of catalytic residue at P2 (P = 0.0095);

MVP

0.71

MPC

1.6

ClinPred

0.63

GERP RS

2.8

PromoterAI

-0.043

Neutral

(source)

Varity_R

0.20

gMVP

0.47

Mutation Taster

=90/10

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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chr7-39950646-C-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over