rs267608554
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2
The NM_001323289.2(CDKL5):c.978-49_978-41delGTGTCAGCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000061 in 1,180,915 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 15 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000018 ( 0 hom., 1 hem., cov: 22)
Exomes 𝑓: 0.000065 ( 0 hom. 14 hem. )
Consequence
CDKL5
NM_001323289.2 intron
NM_001323289.2 intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.61
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 Likely_benign. Variant got -6 ACMG points.
BP6
Variant X-18603851-GTGTGTCAGC-G is Benign according to our data. Variant chrX-18603851-GTGTGTCAGC-G is described in ClinVar as [Likely_benign]. Clinvar id is 189544.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Hemizygotes in GnomAdExome4 at 14 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CDKL5 | NM_001323289.2 | c.978-49_978-41delGTGTCAGCT | intron_variant | ENST00000623535.2 | NP_001310218.1 | |||
CDKL5 | NM_001037343.2 | c.978-49_978-41delGTGTCAGCT | intron_variant | NP_001032420.1 | ||||
CDKL5 | NM_003159.3 | c.978-49_978-41delGTGTCAGCT | intron_variant | NP_003150.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CDKL5 | ENST00000623535.2 | c.978-49_978-41delGTGTCAGCT | intron_variant | 1 | NM_001323289.2 | ENSP00000485244.1 |
Frequencies
GnomAD3 genomes AF: 0.0000179 AC: 2AN: 111916Hom.: 0 Cov.: 22 AF XY: 0.0000293 AC XY: 1AN XY: 34108
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GnomAD3 exomes AF: 0.0000276 AC: 5AN: 180942Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 66832
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GnomAD4 exome AF: 0.0000655 AC: 70AN: 1068999Hom.: 0 AF XY: 0.0000414 AC XY: 14AN XY: 338301
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GnomAD4 genome AF: 0.0000179 AC: 2AN: 111916Hom.: 0 Cov.: 22 AF XY: 0.0000293 AC XY: 1AN XY: 34108
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2Other:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, no assertion criteria provided | curation | RettBASE | Mar 13, 2014 | Unlikely to be pathogenic, not predicted to change splicing; however, there is no empirical evidence for this - |
CDKL5 disorder Benign:1
Likely benign, criteria provided, single submitter | curation | Centre for Population Genomics, CPG | Sep 09, 2024 | This variant has been collected from RettBASE and curated to current modified ACMG/AMP criteria. Based on the classification scheme defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like Disorders Specifications to the ACMG/AMP Variant Interpretation Guidelines VCEP 3.0, this variant is classified as likely benign. At least the following criteria are met: Synonymous or intronic variant outside donor and acceptor splice regions where splicing prediction algorithms do not support significant splicing alteration (spliceAI score <=0.1) (BP4, BP7). - |
not provided Other:1
not provided, flagged submission | literature only | RettBASE | - | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at