rs398123694
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_001323289.2(CDKL5):c.2653G>A(p.Gly885Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000578 in 1,210,322 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. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. G885G) has been classified as Likely benign.
Frequency
Consequence
NM_001323289.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDKL5 | NM_001323289.2 | c.2653G>A | p.Gly885Arg | missense_variant | 18/18 | ENST00000623535.2 | |
CDKL5 | NM_001037343.2 | c.2653G>A | p.Gly885Arg | missense_variant | 19/22 | ||
CDKL5 | NM_003159.3 | c.2653G>A | p.Gly885Arg | missense_variant | 18/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDKL5 | ENST00000623535.2 | c.2653G>A | p.Gly885Arg | missense_variant | 18/18 | 1 | NM_001323289.2 | P1 | |
CDKL5 | ENST00000379989.6 | c.2653G>A | p.Gly885Arg | missense_variant | 19/22 | 1 | |||
CDKL5 | ENST00000379996.7 | c.2653G>A | p.Gly885Arg | missense_variant | 18/21 | 1 | |||
CDKL5 | ENST00000674046.1 | c.2776G>A | p.Gly926Arg | missense_variant | 19/19 |
Frequencies
GnomAD3 genomes ? AF: 0.00000892 AC: 1AN: 112080Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 34250
GnomAD3 exomes AF: 0.00000546 AC: 1AN: 183311Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 67775
GnomAD4 exome AF: 0.00000546 AC: 6AN: 1098242Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 1AN XY: 363596
GnomAD4 genome ? AF: 0.00000892 AC: 1AN: 112080Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 34250
ClinVar
Submissions by phenotype
Developmental and epileptic encephalopathy, 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 08, 2013 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 06, 2022 | The c.2653G>A (p.G885R) alteration is located in exon 18 (coding exon 17) of the CDKL5 gene. This alteration results from a G to A substitution at nucleotide position 2653, causing the glycine (G) at amino acid position 885 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 27, 2013 | - - |
Developmental and epileptic encephalopathy, 2;CN128785:Angelman syndrome-like Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 21, 2022 | 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. 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. ClinVar contains an entry for this variant (Variation ID: 94109). This variant has not been reported in the literature in individuals affected with CDKL5-related conditions. This variant is present in population databases (rs398123694, gnomAD 0.005%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 885 of the CDKL5 protein (p.Gly885Arg). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at