rs786204990
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_001323289.2(CDKL5):c.660_664dup(p.Thr222IlefsTer8) 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 Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 23)
Consequence
CDKL5
NM_001323289.2 frameshift
NM_001323289.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.273
Genes affected
CDKL5 (HGNC:11411): (cyclin dependent kinase like 5) This gene is a member of Ser/Thr protein kinase family and encodes a phosphorylated protein with protein kinase activity. Mutations in this gene have been associated with X-linked infantile spasm syndrome (ISSX), also known as X-linked West syndrome, and Rett syndrome (RTT). Alternate transcriptional splice variants have been characterized. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 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 X-18588058-T-TTTTTA is Pathogenic according to our data. Variant chrX-18588058-T-TTTTTA is described in ClinVar as [Pathogenic]. Clinvar id is 189597.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDKL5 | NM_001323289.2 | c.660_664dup | p.Thr222IlefsTer8 | frameshift_variant | 9/18 | ENST00000623535.2 | |
CDKL5 | NM_001037343.2 | c.660_664dup | p.Thr222IlefsTer8 | frameshift_variant | 10/22 | ||
CDKL5 | NM_003159.3 | c.660_664dup | p.Thr222IlefsTer8 | frameshift_variant | 9/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDKL5 | ENST00000623535.2 | c.660_664dup | p.Thr222IlefsTer8 | frameshift_variant | 9/18 | 1 | NM_001323289.2 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD3 genomes
?
Cov.:
23
GnomAD4 exome Cov.: 29
GnomAD4 exome
Cov.:
29
GnomAD4 genome ? Cov.: 23
GnomAD4 genome
?
Cov.:
23
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Atypical Rett syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | curation | RettBASE | Mar 13, 2014 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at