chrX-18604120-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001323289.2(CDKL5):c.1196A>G(p.Asn399Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001323289.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CDKL5 | NM_001323289.2 | c.1196A>G | p.Asn399Ser | missense_variant | Exon 12 of 18 | ENST00000623535.2 | NP_001310218.1 | |
CDKL5 | NM_001037343.2 | c.1196A>G | p.Asn399Ser | missense_variant | Exon 13 of 22 | NP_001032420.1 | ||
CDKL5 | NM_003159.3 | c.1196A>G | p.Asn399Ser | missense_variant | Exon 12 of 21 | NP_003150.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 23
ClinVar
Submissions by phenotype
Developmental and epileptic encephalopathy, 2;CN128785:Angelman syndrome-like Uncertain:1
This sequence change replaces asparagine with serine at codon 399 of the CDKL5 protein (p.Asn399Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with CDKL5-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CDKL5 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.