7-39950703-A-G

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003718.5(CDK13):c.62A>G(p.Lys21Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000154 in 1,295,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

CDK13
NM_003718.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.45

Publications

5 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: 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=0.11255807).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK13	NM_003718.5 link	c.62A>G	p.Lys21Arg	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.62A>G	p.Lys21Arg	missense_variant	Exon 1 of 14	1	NM_003718.5	ENSP00000181839.4		Q14004-1
CDK13	ENST00000340829.10 link	c.62A>G	p.Lys21Arg	missense_variant	Exon 1 of 14	1		ENSP00000340557.5		Q14004-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000332

AC:

AN:

60218

AF XY:

0.0000290

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000185

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:

0.00000154

AC:

AN:

1295982

Hom.:

Cov.:

AF XY:

0.00000157

AC XY:

AN XY:

637046

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26004

American (AMR)

AF:

0.0000916

AC:

AN:

21842

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21620

East Asian (EAS)

AF:

0.00

AC:

AN:

28324

South Asian (SAS)

AF:

0.00

AC:

AN:

68398

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33934

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3834

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1038348

Other (OTH)

AF:

0.00

AC:

AN:

53678

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Aug 23, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 21 of the CDK13 protein (p.Lys21Arg). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with CDK13-related conditions. Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt CDK13 protein function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.099

T;.

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.027

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.61

T;T

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N

PhyloP100

1.5

PrimateAI

Pathogenic

0.96

PROVEAN

Benign

-0.20

N;N

REVEL

Benign

0.065

Sift

Benign

0.068

T;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.80

P;P

Vest4

0.085

MutPred

0.11

Loss of ubiquitination at K21 (P = 0.0326);Loss of ubiquitination at K21 (P = 0.0326);

MVP

0.30

MPC

1.5

ClinPred

0.26

GERP RS

3.7

PromoterAI

0.13

Neutral

(source)

Varity_R

0.13

gMVP

0.23

Mutation Taster

=96/4

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over