rs267608655

chrX-18619951-GAAGAA-G

Variant summary

Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PVS1 PP5

The NM_001323289.2(CDKL5):c.2363_2367del(p.Lys788IlefsTer11) variant causes a frameshift change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 23)
• Consequence: CDKL5 NM_001323289.2 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.36

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 9 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PP5: Variant X-18619951-GAAGAA-G is Pathogenic according to our data. Variant chrX-18619951-GAAGAA-G is described in ClinVar as [Pathogenic]. Clinvar id is 143802.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDKL5	NM_001323289.2	c.2363_2367del	p.Lys788IlefsTer11	frameshift_variant	16/18	ENST00000623535.2
CDKL5	NM_001037343.2	c.2363_2367del	p.Lys788IlefsTer11	frameshift_variant	17/22
CDKL5	NM_003159.3	c.2363_2367del	p.Lys788IlefsTer11	frameshift_variant	16/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDKL5	ENST00000623535.2	c.2363_2367del	p.Lys788IlefsTer11	frameshift_variant	16/18	1	NM_001323289.2	P1

Frequencies

GnomAD3 genomes Cov.: 23

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 23

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Developmental and epileptic encephalopathy, 2 Pathogenic:1

Pathogenic, no assertion criteria provided

curation

RettBASE

Mar 13, 2014

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs267608655; hg19: chrX-18638071;