Variant X-18564526-GATATATATATAT-GATATATATAT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001323289.2(CDKL5):c.145+27_145+28del variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0538 in 556,775 control chromosomes in the GnomAD database, including 12 homozygotes. There are 400 hemizygotes 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 0.010 ( 5 hom., 203 hem., cov: 19)

Exomes 𝑓: 0.063 ( 7 hom. 197 hem. )

Consequence

CDKL5
NM_001323289.2 splice_donor_5th_base, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.405

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant X-18564526-GAT-G is Benign according to our data. Variant chrX-18564526-GAT-G is described in ClinVar as [Benign]. Clinvar id is 239511.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-18564526-GAT-G is described in Lovd as [Benign]. Variant chrX-18564526-GAT-G is described in Lovd as [Likely_benign].

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
CDKL5	NM_001323289.2 linkuse as main transcript	c.145+27_145+28del	splice_donor_5th_base_variant, intron_variant	ENST00000623535.2	NP_001310218.1
CDKL5	NM_001037343.2 linkuse as main transcript	c.145+27_145+28del	splice_donor_5th_base_variant, intron_variant		NP_001032420.1
CDKL5	NM_003159.3 linkuse as main transcript	c.145+27_145+28del	splice_donor_5th_base_variant, intron_variant		NP_003150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDKL5	ENST00000623535.2 linkuse as main transcript	c.145+27_145+28del		splice_donor_5th_base_variant, intron_variant		1	NM_001323289.2	ENSP00000485244	P1	O76039-2

Frequencies

GnomAD3 genomes

AF:

0.0105

AC:

977

AN:

93107

Hom.:

Cov.:

AF XY:

0.00870

AC XY:

203

AN XY:

23339

show subpopulations

Gnomad AFR

AF:

0.00331

Gnomad AMI

AF:

0.0253

Gnomad AMR

AF:

0.00602

Gnomad ASJ

AF:

0.00431

Gnomad EAS

AF:

0.000337

Gnomad SAS

AF:

0.000485

Gnomad FIN

AF:

0.0302

Gnomad MID

AF:

0.0149

Gnomad NFE

AF:

0.0150

Gnomad OTH

AF:

0.00911

GnomAD3 exomes

AF:

0.0643

AC:

4674

AN:

72668

Hom.:

AF XY:

0.000648

AC XY:

AN XY:

10808

show subpopulations

Gnomad AFR exome

AF:

0.0303

Gnomad AMR exome

AF:

0.0271

Gnomad ASJ exome

AF:

0.0691

Gnomad EAS exome

AF:

0.0222

Gnomad SAS exome

AF:

0.0506

Gnomad FIN exome

AF:

0.193

Gnomad NFE exome

AF:

0.0709

Gnomad OTH exome

AF:

0.0554

GnomAD4 exome

AF:

0.0625

AC:

29001

AN:

463698

Hom.:

AF XY:

0.00206

AC XY:

197

AN XY:

95852

show subpopulations

Gnomad4 AFR exome

AF:

0.0544

Gnomad4 AMR exome

AF:

0.0362

Gnomad4 ASJ exome

AF:

0.0658

Gnomad4 EAS exome

AF:

0.0855

Gnomad4 SAS exome

AF:

0.0255

Gnomad4 FIN exome

AF:

0.0979

Gnomad4 NFE exome

AF:

0.0635

Gnomad4 OTH exome

AF:

0.0675

GnomAD4 genome

AF:

0.0105

AC:

977

AN:

93077

Hom.:

Cov.:

AF XY:

0.00870

AC XY:

203

AN XY:

23337

show subpopulations

Gnomad4 AFR

AF:

0.00331

Gnomad4 AMR

AF:

0.00602

Gnomad4 ASJ

AF:

0.00431

Gnomad4 EAS

AF:

0.000339

Gnomad4 SAS

AF:

0.000490

Gnomad4 FIN

AF:

0.0302

Gnomad4 NFE

AF:

0.0150

Gnomad4 OTH

AF:

0.00904

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 13, 2019

- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

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.

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