Genetic Variant CDKL5:c.145+25_145+28delATAT (chrX-18564526-GATAT-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS1

The ENST00000623535.2(CDKL5):c.145+5_145+8delATAT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0039 in 594,491 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.000043 ( 0 hom., 0 hem., cov: 19)

Exomes 𝑓: 0.0046 ( 0 hom. 0 hem. )

Consequence

CDKL5
ENST00000623535.2 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.740

Variant links:

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]

CDKL5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant X-18564526-GATAT-G is Benign according to our data. Variant chrX-18564526-GATAT-G is described in ClinVar as [Benign]. Clinvar id is 1168486.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.00462 (2317/501268) while in subpopulation EAS AF= 0.008 (149/18631). AF 95% confidence interval is 0.00695. There are 0 homozygotes in gnomad4_exome. There are 0 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CDKL5	NM_001323289.2 link	c.145+25_145+28delATAT	intron_variant	Intron 4 of 17	ENST00000623535.2	NP_001310218.1	O76039-2
CDKL5	NM_001037343.2 link	c.145+25_145+28delATAT	intron_variant	Intron 5 of 21		NP_001032420.1	O76039-1
CDKL5	NM_003159.3 link	c.145+25_145+28delATAT	intron_variant	Intron 4 of 20		NP_003150.1	O76039-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKL5	ENST00000623535.2 link	c.145+5_145+8delATAT		splice_region_variant, intron_variant	Intron 4 of 17	1	NM_001323289.2	ENSP00000485244.1		O76039-2

Frequencies

GnomAD3 genomes

AF:

0.0000429

AC:

AN:

93248

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

23402

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000120

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000285

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000431

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00334

AC:

243

AN:

72668

Hom.:

AF XY:

0.00

AC XY:

AN XY:

10808

show subpopulations

Gnomad AFR exome

AF:

0.00474

Gnomad AMR exome

AF:

0.00310

Gnomad ASJ exome

AF:

0.00180

Gnomad EAS exome

AF:

0.00212

Gnomad SAS exome

AF:

0.00309

Gnomad FIN exome

AF:

0.00472

Gnomad NFE exome

AF:

0.00340

Gnomad OTH exome

AF:

0.00254

GnomAD4 exome

AF:

0.00462

AC:

2317

AN:

501268

Hom.:

AF XY:

0.00

AC XY:

AN XY:

120376

show subpopulations

Gnomad4 AFR exome

AF:

0.00520

Gnomad4 AMR exome

AF:

0.00345

Gnomad4 ASJ exome

AF:

0.00564

Gnomad4 EAS exome

AF:

0.00800

Gnomad4 SAS exome

AF:

0.00206

Gnomad4 FIN exome

AF:

0.00465

Gnomad4 NFE exome

AF:

0.00456

Gnomad4 OTH exome

AF:

0.00626

GnomAD4 genome

AF:

0.0000429

AC:

AN:

93223

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

23403

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000120

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000285

Gnomad4 NFE

AF:

0.0000431

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: 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

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

X-18564526-GATATATATATATAT-GATATATATAT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over