rs62643617
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001323289.2(CDKL5):āc.2378T>Cā(p.Val793Ala) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00001 in 1,095,234 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V793I) has been classified as Uncertain significance.
Frequency
Consequence
NM_001323289.2 missense, splice_region
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.2378T>C | p.Val793Ala | missense_variant, splice_region_variant | 17/18 | ENST00000623535.2 | |
CDKL5 | NM_001037343.2 | c.2378T>C | p.Val793Ala | missense_variant, splice_region_variant | 18/22 | ||
CDKL5 | NM_003159.3 | c.2378T>C | p.Val793Ala | missense_variant, splice_region_variant | 17/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDKL5 | ENST00000623535.2 | c.2378T>C | p.Val793Ala | missense_variant, splice_region_variant | 17/18 | 1 | NM_001323289.2 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 22
GnomAD3 exomes AF: 0.00000547 AC: 1AN: 182886Hom.: 0 AF XY: 0.0000148 AC XY: 1AN XY: 67408
GnomAD4 exome AF: 0.0000100 AC: 11AN: 1095234Hom.: 0 Cov.: 29 AF XY: 0.0000194 AC XY: 7AN XY: 360830
GnomAD4 genome ? Cov.: 22
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, no assertion criteria provided | curation | RettBASE | Mar 13, 2014 | Not a conserved amino acid residue, sidechain effects likely to be conservative; no parental DNA available for testing; In silico prediction: SIFT = deleterious, MutationTaster = disease-causing, PolyPhen2 = possibly damaging, AlignGVGD = benign (C0) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at