7-39950820-TC-T
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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
NM_003718.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.72
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 |
---|---|---|---|---|---|---|---|
CDK13 | NM_003718.5 | c.181del | p.Leu61TrpfsTer80 | frameshift_variant | 1/14 | ENST00000181839.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDK13 | ENST00000181839.10 | c.181del | p.Leu61TrpfsTer80 | frameshift_variant | 1/14 | 1 | NM_003718.5 | P3 | |
CDK13 | ENST00000340829.10 | c.181del | p.Leu61TrpfsTer80 | frameshift_variant | 1/14 | 1 | A1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 33
GnomAD4 exome
Cov.:
33
GnomAD4 genome Cov.: 32
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 submitter | clinical testing | Ambry Genetics | Aug 16, 2023 | The 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 submitter | clinical testing | Undiagnosed Diseases Network, NIH | Mar 07, 2019 | - - |
Computational scores
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at