chrX-18425831-T-C
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_001323289.2(CDKL5):c.-163+136T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0131 in 112,405 control chromosomes in the GnomAD database, including 12 homozygotes. There are 413 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.013 ( 12 hom., 411 hem., cov: 24)
Exomes 𝑓: 0.015 ( 0 hom. 2 hem. )
Consequence
CDKL5
NM_001323289.2 intron
NM_001323289.2 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.262
Genes affected
CDKL5 (HGNC:11411): (cyclin dependent kinase like 5) This gene is a member of Ser/Thr protein kinase family and encodes a phosphorylated protein with protein kinase activity. Mutations in this gene have been associated with X-linked infantile spasm syndrome (ISSX), also known as X-linked West syndrome, and Rett syndrome (RTT). Alternate transcriptional splice variants have been characterized. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
?
Variant X-18425831-T-C is Benign according to our data. Variant chrX-18425831-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1189327.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0131 (1469/112271) while in subpopulation AFR AF= 0.0331 (1026/31002). AF 95% confidence interval is 0.0314. There are 12 homozygotes in gnomad4. There are 411 alleles in male gnomad4 subpopulation. Median coverage is 24. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 12 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDKL5 | NM_001323289.2 | c.-163+136T>C | intron_variant | ENST00000623535.2 | |||
CDKL5 | NM_003159.3 | c.-163+136T>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDKL5 | ENST00000623535.2 | c.-163+136T>C | intron_variant | 1 | NM_001323289.2 | P1 | |||
CDKL5 | ENST00000379996.7 | c.-163+136T>C | intron_variant | 1 | |||||
CDKL5 | ENST00000674046.1 | c.-163+136T>C | intron_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0131 AC: 1471AN: 112229Hom.: 12 Cov.: 24 AF XY: 0.0120 AC XY: 413AN XY: 34517
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GnomAD4 exome AF: 0.0149 AC: 2AN: 134Hom.: 0 AF XY: 0.0286 AC XY: 2AN XY: 70
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 08, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at