rs267606713
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PM5PP3_ModeratePP5
The NM_001323289.2(CDKL5):c.863C>T(p.Thr288Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T288R) has been classified as Likely pathogenic.
Frequency
Consequence
NM_001323289.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDKL5 | NM_001323289.2 | c.863C>T | p.Thr288Ile | missense_variant | 11/18 | ENST00000623535.2 | |
CDKL5 | NM_001037343.2 | c.863C>T | p.Thr288Ile | missense_variant | 12/22 | ||
CDKL5 | NM_003159.3 | c.863C>T | p.Thr288Ile | missense_variant | 11/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDKL5 | ENST00000623535.2 | c.863C>T | p.Thr288Ile | missense_variant | 11/18 | 1 | NM_001323289.2 | P1 |
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD4 exome Cov.: 28
GnomAD4 genome Cov.: 23
ClinVar
Submissions by phenotype
Developmental and epileptic encephalopathy, 2 Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 23, 2008 | - - |
Pathogenic, no assertion criteria provided | curation | RettBASE | Mar 13, 2014 | Highly conserved residue, not found in healthy mother of affected son; In silico prediction: SIFT = deleterious, MutationTaster = disease-causing, PolyPhen2 = possibly damaging, AlignGVGD = benign (C0) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at