X-18564526-GATATATATATATAT-GATATATATATATATATATAT

Variant names:

• chrX-18564526-G-GATATAT
• rs745969938
• NM_001323289.2:c.145+23_145+28dupATATAT

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS1

The ENST00000623535.2(CDKL5):​c.145+4_145+5insATATAT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 19)
  • Exomes 𝑓: 0.000057 (0 hom. 0 hem.)
• Consequence: CDKL5 ENST00000623535.2 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.405

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_benign. Variant got -6 ACMG points.

• BP6: Variant X-18564526-G-GATATAT is Benign according to our data. Variant chrX-18564526-G-GATATAT is described in ClinVar as [Likely_benign]. Clinvar id is 1615526.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0000566 (29/512819) while in subpopulation MID AF= 0.0005 (1/2001). AF 95% confidence interval is 0.0000422. There are 0 homozygotes in gnomad4_exome. There are 0 alleles in male gnomad4_exome subpopulation. Median coverage is 5. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKL5	NM_001323289.2	c.145+23_145+28dupATATAT		intron_variant	Intron 4 of 17	ENST00000623535.2	NP_001310218.1
CDKL5	NM_001037343.2	c.145+23_145+28dupATATAT		intron_variant	Intron 5 of 21		NP_001032420.1
CDKL5	NM_003159.3	c.145+23_145+28dupATATAT		intron_variant	Intron 4 of 20		NP_003150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKL5	ENST00000623535.2	c.145+4_145+5insATATAT		splice_region_variant, intron_variant	Intron 4 of 17	1	NM_001323289.2	ENSP00000485244.1

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD4 exome AF: 0.0000566 AC: 29 AN: 512819 Hom.: 0 Cov.: 5 AF XY: 0.00 AC XY: 0 AN XY: 125309

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000156

Gnomad4 SAS exome AF: 0.0000343

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000612

Gnomad4 OTH exome AF: 0.0000847

GnomAD4 genome Cov.: 19

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Developmental and epileptic encephalopathy, 2;CN128785:Angelman syndrome-like Benign:1

Jan 05, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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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: rs745969938; hg19: chrX-18582646;