rs1485485459
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001323289.2(CDKL5):āc.2490G>Cā(p.Gln830His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000913 in 109,551 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDKL5 | NM_001323289.2 | c.2490G>C | p.Gln830His | missense_variant | 17/18 | ENST00000623535.2 | |
CDKL5 | NM_001037343.2 | c.2490G>C | p.Gln830His | missense_variant | 18/22 | ||
CDKL5 | NM_003159.3 | c.2490G>C | p.Gln830His | missense_variant | 17/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDKL5 | ENST00000623535.2 | c.2490G>C | p.Gln830His | missense_variant | 17/18 | 1 | NM_001323289.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000913 AC: 1AN: 109551Hom.: 0 Cov.: 21 AF XY: 0.0000314 AC XY: 1AN XY: 31831
GnomAD4 exome Cov.: 30
GnomAD4 genome ? AF: 0.00000913 AC: 1AN: 109551Hom.: 0 Cov.: 21 AF XY: 0.0000314 AC XY: 1AN XY: 31831
ClinVar
Submissions by phenotype
Developmental and epileptic encephalopathy, 2;CN128785:Angelman syndrome-like Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 25, 2018 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with CDKL5-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamine with histidine at codon 830 of the CDKL5 protein (p.Gln830His). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and histidine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at