rs781774964
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_001323289.2(CDKL5):c.2541G>A(p.Ser847=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000281 in 1,209,654 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 13 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 0.0000090 ( 0 hom., 0 hem., cov: 22)
Exomes 𝑓: 0.000030 ( 0 hom. 13 hem. )
Consequence
CDKL5
NM_001323289.2 synonymous
NM_001323289.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.41
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 -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
?
Variant X-18628415-G-A is Benign according to our data. Variant chrX-18628415-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 533392.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-1.41 with no splicing effect.
BS2
?
High Hemizygotes in GnomAdExome4 at 13 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDKL5 | NM_001323289.2 | c.2541G>A | p.Ser847= | synonymous_variant | 18/18 | ENST00000623535.2 | |
CDKL5 | NM_001037343.2 | c.2541G>A | p.Ser847= | synonymous_variant | 19/22 | ||
CDKL5 | NM_003159.3 | c.2541G>A | p.Ser847= | synonymous_variant | 18/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDKL5 | ENST00000623535.2 | c.2541G>A | p.Ser847= | synonymous_variant | 18/18 | 1 | NM_001323289.2 | P1 | |
CDKL5 | ENST00000379989.6 | c.2541G>A | p.Ser847= | synonymous_variant | 19/22 | 1 | |||
CDKL5 | ENST00000379996.7 | c.2541G>A | p.Ser847= | synonymous_variant | 18/21 | 1 | |||
CDKL5 | ENST00000674046.1 | c.2664G>A | p.Ser888= | synonymous_variant | 19/19 |
Frequencies
GnomAD3 genomes ? AF: 0.00000895 AC: 1AN: 111688Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 33902
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GnomAD3 exomes AF: 0.0000654 AC: 12AN: 183435Hom.: 0 AF XY: 0.0000737 AC XY: 5AN XY: 67865
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GnomAD4 exome AF: 0.0000301 AC: 33AN: 1097966Hom.: 0 Cov.: 32 AF XY: 0.0000358 AC XY: 13AN XY: 363322
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GnomAD4 genome ? AF: 0.00000895 AC: 1AN: 111688Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 33902
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2018 | - - |
Developmental and epileptic encephalopathy, 2;CN128785:Angelman syndrome-like Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Oct 19, 2022 | - - |
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