rs891117762
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_001323289.2(CDKL5):āc.1590A>Cā(p.Pro530=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000413 in 1,209,657 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ).
Frequency
Genomes: š 0.0000090 ( 0 hom., 0 hem., cov: 23)
Exomes š: 0.0000036 ( 0 hom. 3 hem. )
Consequence
CDKL5
NM_001323289.2 synonymous
NM_001323289.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0970
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 -11 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
?
Variant X-18604514-A-C is Benign according to our data. Variant chrX-18604514-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 533397.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.097 with no splicing effect.
BS2
?
High Hemizygotes in GnomAdExome4 at 3 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDKL5 | NM_001323289.2 | c.1590A>C | p.Pro530= | synonymous_variant | 12/18 | ENST00000623535.2 | |
CDKL5 | NM_001037343.2 | c.1590A>C | p.Pro530= | synonymous_variant | 13/22 | ||
CDKL5 | NM_003159.3 | c.1590A>C | p.Pro530= | synonymous_variant | 12/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDKL5 | ENST00000623535.2 | c.1590A>C | p.Pro530= | synonymous_variant | 12/18 | 1 | NM_001323289.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000897 AC: 1AN: 111469Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 33655
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GnomAD4 exome AF: 0.00000364 AC: 4AN: 1098188Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 3AN XY: 363544
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GnomAD4 genome ? AF: 0.00000897 AC: 1AN: 111469Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 33655
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Developmental and epileptic encephalopathy, 2;CN128785:Angelman syndrome-like Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 10, 2017 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at