X-18575384-G-A
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PM1PM2PM5PP3_StrongPP5_Moderate
The NM_001323289.2(CDKL5):c.176G>A(p.Arg59Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000894 in 111,918 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R59P) has been classified as Likely pathogenic.
Frequency
Consequence
NM_001323289.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDKL5 | NM_001323289.2 | c.176G>A | p.Arg59Gln | missense_variant | 5/18 | ENST00000623535.2 | |
CDKL5 | NM_001037343.2 | c.176G>A | p.Arg59Gln | missense_variant | 6/22 | ||
CDKL5 | NM_003159.3 | c.176G>A | p.Arg59Gln | missense_variant | 5/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDKL5 | ENST00000623535.2 | c.176G>A | p.Arg59Gln | missense_variant | 5/18 | 1 | NM_001323289.2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000894 AC: 1AN: 111918Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 34100
GnomAD4 exome Cov.: 28
GnomAD4 genome AF: 0.00000894 AC: 1AN: 111918Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 34100
ClinVar
Submissions by phenotype
Developmental and epileptic encephalopathy, 2 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Equipe Genetique des Anomalies du Developpement, Université de Bourgogne | Aug 15, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at