X-18507113-T-C
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_001323289.2(CDKL5):āc.17T>Cā(p.Ile6Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000644 in 1,087,577 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I6V) has been classified as Uncertain significance.
Frequency
Consequence
NM_001323289.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDKL5 | NM_001323289.2 | c.17T>C | p.Ile6Thr | missense_variant | 2/18 | ENST00000623535.2 | |
CDKL5 | NM_001037343.2 | c.17T>C | p.Ile6Thr | missense_variant | 3/22 | ||
CDKL5 | NM_003159.3 | c.17T>C | p.Ile6Thr | missense_variant | 2/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDKL5 | ENST00000623535.2 | c.17T>C | p.Ile6Thr | missense_variant | 2/18 | 1 | NM_001323289.2 | P1 |
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD3 exomes AF: 0.0000109 AC: 2AN: 183320Hom.: 0 AF XY: 0.0000148 AC XY: 1AN XY: 67776
GnomAD4 exome AF: 0.00000644 AC: 7AN: 1087577Hom.: 0 Cov.: 26 AF XY: 0.0000113 AC XY: 4AN XY: 353751
GnomAD4 genome Cov.: 23
ClinVar
Submissions by phenotype
Developmental and epileptic encephalopathy, 2;CN128785:Angelman syndrome-like Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 09, 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with CDKL5-related conditions. This variant is present in population databases (rs746036179, gnomAD 0.005%), including at least one homozygous and/or hemizygous individual. This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 6 of the CDKL5 protein (p.Ile6Thr). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at