rs587783084
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PS1PM1PM2PM5PP3_StrongPP5_Moderate
The NM_001323289.2(CDKL5):c.526T>A(p.Trp176Arg) 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 Likely pathogenic (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. W176G) has been classified as Pathogenic.
Frequency
Consequence
NM_001323289.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDKL5 | NM_001323289.2 | c.526T>A | p.Trp176Arg | missense_variant | 8/18 | ENST00000623535.2 | |
CDKL5 | NM_001037343.2 | c.526T>A | p.Trp176Arg | missense_variant | 9/22 | ||
CDKL5 | NM_003159.3 | c.526T>A | p.Trp176Arg | missense_variant | 8/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDKL5 | ENST00000623535.2 | c.526T>A | p.Trp176Arg | missense_variant | 8/18 | 1 | NM_001323289.2 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 22
GnomAD4 exome Cov.: 28
GnomAD4 genome ? Cov.: 22
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Jul 20, 2021 | Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports a deleterious effect on splicing; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 29655203) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at