rs267608658
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_001323289.2(CDKL5):c.2377-31T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 1,193,965 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).
Frequency
Genomes: 𝑓 0.000036 ( 0 hom., 2 hem., cov: 22)
Exomes 𝑓: 0.000025 ( 0 hom. 8 hem. )
Consequence
CDKL5
NM_001323289.2 intron
NM_001323289.2 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.417
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 -9 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
?
Variant X-18625097-T-C is Benign according to our data. Variant chrX-18625097-T-C is described in ClinVar as [Benign]. Clinvar id is 156083.Status of the report is no_assertion_criteria_provided, 0 stars.
BS2
?
High Hemizygotes in GnomAd at 2 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDKL5 | NM_001323289.2 | c.2377-31T>C | intron_variant | ENST00000623535.2 | |||
CDKL5 | NM_001037343.2 | c.2377-31T>C | intron_variant | ||||
CDKL5 | NM_003159.3 | c.2377-31T>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDKL5 | ENST00000623535.2 | c.2377-31T>C | intron_variant | 1 | NM_001323289.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000361 AC: 4AN: 110760Hom.: 0 Cov.: 22 AF XY: 0.0000607 AC XY: 2AN XY: 32928
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00000548 AC: 1AN: 182532Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 67154
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GnomAD4 exome AF: 0.0000249 AC: 27AN: 1083205Hom.: 0 Cov.: 27 AF XY: 0.0000229 AC XY: 8AN XY: 350071
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GnomAD4 genome ? AF: 0.0000361 AC: 4AN: 110760Hom.: 0 Cov.: 22 AF XY: 0.0000607 AC XY: 2AN XY: 32928
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ClinVar
Significance: Benign
Submissions summary: Benign:1Other:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, no assertion criteria provided | curation | RettBASE | May 09, 2014 | - - |
not provided Other:1
not provided, flagged submission | literature only | RettBASE | - | - - |
Computational scores
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Name
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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