rs1555951997
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2_SupportingPM4_Supporting
This summary comes from the ClinGen Evidence Repository: The p.Lys432_Tyr433delinsAsn variant in CDKL5 is absent from gnomAD (PM2_supporting). The p.Lys432_Tyr433delinsAsn variant causes a change in the length of 1 amino acid in the protein due to an in-frame deletion or insertion in a non-repeat region of CDKL5 (PM4_supporting). In summary, p.Lys432_Tyr433delinsAsn variant in CDKL5 is classified as a variant of uncertain significance based on the ACMG/AMP criteria (PM2_supporting, PM4_supporting). LINK:https://erepo.genome.network/evrepo/ui/classification/CA645373290/MONDO:0100039/016
Frequency
Consequence
NM_001323289.2 inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDKL5 | NM_001323289.2 | c.1296_1298del | p.Lys432_Tyr433delinsAsn | inframe_deletion | 12/18 | ENST00000623535.2 | |
CDKL5 | NM_001037343.2 | c.1296_1298del | p.Lys432_Tyr433delinsAsn | inframe_deletion | 13/22 | ||
CDKL5 | NM_003159.3 | c.1296_1298del | p.Lys432_Tyr433delinsAsn | inframe_deletion | 12/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDKL5 | ENST00000623535.2 | c.1296_1298del | p.Lys432_Tyr433delinsAsn | inframe_deletion | 12/18 | 1 | NM_001323289.2 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 22
GnomAD4 genome ? Cov.: 22
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 12, 2015 | - - |
CDKL5 disorder Uncertain:1
Uncertain significance, reviewed by expert panel | curation | ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel | Mar 26, 2021 | The p.Lys432_Tyr433delinsAsn variant in CDKL5 is absent from gnomAD (PM2_supporting). The p.Lys432_Tyr433delinsAsn variant causes a change in the length of 1 amino acid in the protein due to an in-frame deletion or insertion in a non-repeat region of CDKL5 (PM4_supporting). In summary, p.Lys432_Tyr433delinsAsn variant in CDKL5 is classified as a variant of uncertain significance based on the ACMG/AMP criteria (PM2_supporting, PM4_supporting). - |
Developmental and epileptic encephalopathy, 2;CN128785:Angelman syndrome-like Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 31, 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 434662). This variant has not been reported in the literature in individuals affected with CDKL5-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant, c.1296_1298del, results in the deletion of one amino acid(s) of the CDKL5 protein (p.Lys432_Tyr433delinsAsn), but otherwise preserves the integrity of the reading frame. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at