rs1279388510
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001323289.2(CDKL5):c.1094G>A(p.Ser365Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000331 in 1,209,363 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S365T) 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 -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDKL5 | NM_001323289.2 | c.1094G>A | p.Ser365Asn | missense_variant | 12/18 | ENST00000623535.2 | |
CDKL5 | NM_001037343.2 | c.1094G>A | p.Ser365Asn | missense_variant | 13/22 | ||
CDKL5 | NM_003159.3 | c.1094G>A | p.Ser365Asn | missense_variant | 12/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDKL5 | ENST00000623535.2 | c.1094G>A | p.Ser365Asn | missense_variant | 12/18 | 1 | NM_001323289.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000180 AC: 2AN: 111109Hom.: 0 Cov.: 23 AF XY: 0.0000600 AC XY: 2AN XY: 33339
GnomAD3 exomes AF: 0.0000109 AC: 2AN: 183462Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 67892
GnomAD4 exome AF: 0.00000182 AC: 2AN: 1098202Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 363556
GnomAD4 genome ? AF: 0.0000180 AC: 2AN: 111161Hom.: 0 Cov.: 23 AF XY: 0.0000599 AC XY: 2AN XY: 33401
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2023 | CDKL5: PM2 - |
Developmental and epileptic encephalopathy, 2;CN128785:Angelman syndrome-like Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 11, 2023 | This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 365 of the CDKL5 protein (p.Ser365Asn). This variant is present in population databases (no rsID available, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with CDKL5-related conditions. ClinVar contains an entry for this variant (Variation ID: 1503908). 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 with a negative predictive value of 95%. 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