rs267608623
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM2_SupportingPVS1PM6
This summary comes from the ClinGen Evidence Repository: The c.1311dup variant in CDKL5 is predicted to cause a premature stop codon that leads to a truncated or absent protein in a gene where loss-of-function is an established mechanism. There is significant evidence that loss of this region of the gene is pathogenic (PVS1). The c.1311dup variant in CDKL5 has been reported as a de novo occurrence (biological parentage unconfirmed) in an individual with early onset seizures and infantile spasms (PMID 19793311) (PM6). The c.1311dup variant in CDKL5 is absent from gnomAD v2.1.1 (PM2_supporting). In summary, the c.1311dup variant in CDKL5 is classified as pathogenic for a CDKL5-related disorder based on the ACMG/AMP criteria (PVS1, PM6, PM2_supporting). LINK:https://erepo.genome.network/evrepo/ui/classification/CA170444/MONDO:0100039/034
Frequency
Consequence
NM_001323289.2 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDKL5 | NM_001323289.2 | c.1311dup | p.Ser438GlnfsTer25 | frameshift_variant | 12/18 | ENST00000623535.2 | |
CDKL5 | NM_001037343.2 | c.1311dup | p.Ser438GlnfsTer25 | frameshift_variant | 13/22 | ||
CDKL5 | NM_003159.3 | c.1311dup | p.Ser438GlnfsTer25 | frameshift_variant | 12/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDKL5 | ENST00000623535.2 | c.1311dup | p.Ser438GlnfsTer25 | frameshift_variant | 12/18 | 1 | NM_001323289.2 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD4 exome Cov.: 32
GnomAD4 genome ? Cov.: 23
ClinVar
Submissions by phenotype
CDKL5 disorder Pathogenic:1
Pathogenic, reviewed by expert panel | curation | ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel | Apr 18, 2024 | The c.1311dup variant in CDKL5 is predicted to cause a premature stop codon that leads to a truncated or absent protein in a gene where loss-of-function is an established mechanism. There is significant evidence that loss of this region of the gene is pathogenic (PVS1). The c.1311dup variant in CDKL5 has been reported as a de novo occurrence (biological parentage unconfirmed) in an individual with early onset seizures and infantile spasms (PMID 19793311) (PM6). The c.1311dup variant in CDKL5 is absent from gnomAD v2.1.1 (PM2_supporting). In summary, the c.1311dup variant in CDKL5 is classified as pathogenic for a CDKL5-related disorder based on the ACMG/AMP criteria (PVS1, PM6, PM2_supporting). - |
Atypical Rett syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | curation | RettBASE | Mar 13, 2014 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at