rs150844616
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The ENST00000623535.2(CDKL5):c.1332C>T(p.Arg444=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00039 in 1,210,299 control chromosomes in the GnomAD database, including 1 homozygotes. There are 127 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 0.0018 ( 0 hom., 53 hem., cov: 22)
Exomes 𝑓: 0.00024 ( 1 hom. 74 hem. )
Consequence
CDKL5
ENST00000623535.2 synonymous
ENST00000623535.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0440
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 -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
Variant X-18604256-C-T is Benign according to our data. Variant chrX-18604256-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 136711.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-18604256-C-T is described in Lovd as [Likely_benign]. Variant chrX-18604256-C-T is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-0.044 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00182 (204/112126) while in subpopulation AFR AF= 0.00599 (185/30880). AF 95% confidence interval is 0.00528. There are 0 homozygotes in gnomad4. There are 53 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.
BS2
High Hemizygotes in GnomAd4 at 53 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CDKL5 | NM_001323289.2 | c.1332C>T | p.Arg444= | synonymous_variant | 12/18 | ENST00000623535.2 | NP_001310218.1 | |
CDKL5 | NM_001037343.2 | c.1332C>T | p.Arg444= | synonymous_variant | 13/22 | NP_001032420.1 | ||
CDKL5 | NM_003159.3 | c.1332C>T | p.Arg444= | synonymous_variant | 12/21 | NP_003150.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CDKL5 | ENST00000623535.2 | c.1332C>T | p.Arg444= | synonymous_variant | 12/18 | 1 | NM_001323289.2 | ENSP00000485244 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00182 AC: 204AN: 112071Hom.: 0 Cov.: 22 AF XY: 0.00155 AC XY: 53AN XY: 34223
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GnomAD3 exomes AF: 0.000529 AC: 97AN: 183300Hom.: 0 AF XY: 0.000339 AC XY: 23AN XY: 67784
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GnomAD4 exome AF: 0.000244 AC: 268AN: 1098173Hom.: 1 Cov.: 32 AF XY: 0.000204 AC XY: 74AN XY: 363531
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GnomAD4 genome AF: 0.00182 AC: 204AN: 112126Hom.: 0 Cov.: 22 AF XY: 0.00155 AC XY: 53AN XY: 34288
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:5
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 16, 2013 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Aug 10, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Feb 11, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Mar 29, 2017 | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
History of neurodevelopmental disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 30, 2016 | Synonymous alterations with insufficient evidence to classify as benign - |
Developmental and epileptic encephalopathy, 2;CN128785:Angelman syndrome-like Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at