7-39950702-A-T

Variant names:

• chr7-39950702-A-T
• NM_003718.5:c.61A>T

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_003718.5(CDK13):​c.61A>T​(p.Lys21*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000773 in 1,294,006 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 Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.7e-7 (0 hom.)
• Consequence: CDK13 NM_003718.5 stop_gained
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1 U:1
• Conservation: PhyloP100: 1.75
• Publications: 0 publications found

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

ACMG classification

Our verdict: Pathogenic. The variant received 11 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 90 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 7-39950702-A-T is Pathogenic according to our data. Variant chr7-39950702-A-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 3670622.We mark this variant Likely_pathogenic, oryginal submissions are: {Uncertain_significance=1, Pathogenic=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK13	NM_003718.5	c.61A>T	p.Lys21*	stop_gained	Exon 1 of 14	ENST00000181839.10	NP_003709.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK13	ENST00000181839.10	c.61A>T	p.Lys21*	stop_gained	Exon 1 of 14	1	NM_003718.5	ENSP00000181839.4
CDK13	ENST00000340829.10	c.61A>T	p.Lys21*	stop_gained	Exon 1 of 14	1		ENSP00000340557.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.73e-7 AC: 1 AN: 1294006 Hom.: 0 Cov.: 34 AF XY: 0.00000157 AC XY: 1 AN XY: 635940

African (AFR) AF: 0.00 AC: 0 AN: 25964

American (AMR) AF: 0.00 AC: 0 AN: 21572

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21498

East Asian (EAS) AF: 0.00 AC: 0 AN: 28284

South Asian (SAS) AF: 0.00 AC: 0 AN: 68146

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33870

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3822

European-Non Finnish (NFE) AF: 9.64e-7 AC: 1 AN: 1037242

Other (OTH) AF: 0.00 AC: 0 AN: 53608

GnomAD4 genome Cov.: 32

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:1 Uncertain:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Pathogenic:1

Oct 30, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change creates a premature translational stop signal (p.Lys21*) in the CDK13 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CDK13 are known to be pathogenic (PMID: 27479907, 29021403, 29393965). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CDK13-related conditions. For these reasons, this variant has been classified as Pathogenic. -

Congenital heart defects, dysmorphic facial features, and intellectual developmental disorder Uncertain:1

Apr 19, 2025

Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ACMG classification criteria: PVS1 strong, PM2 supporting -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.53	D
BayesDel_noAF	Pathogenic	0.53
CADD	Pathogenic	38
DANN	Uncertain	0.99
Eigen	Pathogenic	0.78
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Benign	0.41	N
PhyloP100		1.7
Vest4		0.074
GERP RS		3.7
PromoterAI		0.029	Neutral
Mutation Taster		=7/193	disease causing (fs/PTC)

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

Other links and lift over

hg19: chr7-39990301;