7-39950820-TC-T

Variant summary

Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong

The NM_003718.5(CDK13):​c.181del​(p.Leu61TrpfsTer80) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)

Consequence

CDK13
NM_003718.5 frameshift

Scores

Not classified

Clinical Significance

Pathogenic/Likely pathogenic criteria provided, multiple submitters, no conflicts P:2

Conservation

PhyloP100: 2.72
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]

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 18 ACMG points.

PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 7-39950820-TC-T is Pathogenic according to our data. Variant chr7-39950820-TC-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 521173.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-39950820-TC-T is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CDK13NM_003718.5 linkuse as main transcriptc.181del p.Leu61TrpfsTer80 frameshift_variant 1/14 ENST00000181839.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CDK13ENST00000181839.10 linkuse as main transcriptc.181del p.Leu61TrpfsTer80 frameshift_variant 1/141 NM_003718.5 P3Q14004-1
CDK13ENST00000340829.10 linkuse as main transcriptc.181del p.Leu61TrpfsTer80 frameshift_variant 1/141 A1Q14004-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Inborn genetic diseases Pathogenic:1
Pathogenic, criteria provided, single submitterclinical testingAmbry GeneticsAug 16, 2023The c.181delC (p.L61Wfs*80) alteration, located in exon 1 (coding exon 1) of the CDK13 gene, consists of a deletion of one nucleotide at position 181, causing a translational frameshift with a predicted alternate stop codon after 80 amino acids. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This variant has been determined to be the result of a de novo mutation in one individual with features consistent with CDK13-related neurodevelopmental disorder (Lee, 2020). Based on the available evidence, this alteration is classified as pathogenic. -
Congenital heart defects, dysmorphic facial features, and intellectual developmental disorder Pathogenic:1
Likely pathogenic, criteria provided, single submitterclinical testingUndiagnosed Diseases Network, NIHMar 07, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1554317002; hg19: chr7-39990419; API