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

Variant summary

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

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

Frequency

Genomes: 𝑓 0.012 ( 4 hom., 177 hem., cov: 19)

Exomes 𝑓: 0.061 ( 0 hom. 55 hem. )

Consequence

CDKL5
ENST00000623535.2 splice_region, 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-G-GAT is Benign according to our data. Variant chrX-18564526-G-GAT is described in ClinVar as [Benign]. Clinvar id is 414804.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
CDKL5	NM_001323289.2 link	c.145+27_145+28dupAT	intron_variant	ENST00000623535.2	NP_001310218.1	O76039-2
CDKL5	NM_001037343.2 link	c.145+27_145+28dupAT	intron_variant		NP_001032420.1	O76039-1
CDKL5	NM_003159.3 link	c.145+27_145+28dupAT	intron_variant		NP_003150.1	O76039-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDKL5	ENST00000623535.2 link	c.145+4_145+5insAT		splice_region_variant, intron_variant		1	NM_001323289.2	ENSP00000485244.1		O76039-2

Frequencies

GnomAD3 genomes

AF:

0.0123

AC:

1140

AN:

93017

Hom.:

Cov.:

AF XY:

0.00763

AC XY:

178

AN XY:

23319

show subpopulations

Gnomad AFR

AF:

0.0146

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0159

Gnomad ASJ

AF:

0.00388

Gnomad EAS

AF:

0.0159

Gnomad SAS

AF:

0.0204

Gnomad FIN

AF:

0.00949

Gnomad MID

AF:

0.00498

Gnomad NFE

AF:

0.0103

Gnomad OTH

AF:

0.0190

GnomAD3 exomes

AF:

0.0517

AC:

3755

AN:

72668

Hom.:

AF XY:

0.000463

AC XY:

AN XY:

10808

show subpopulations

Gnomad AFR exome

AF:

0.0103

Gnomad AMR exome

AF:

0.0266

Gnomad ASJ exome

AF:

0.0937

Gnomad EAS exome

AF:

0.0224

Gnomad SAS exome

AF:

0.0833

Gnomad FIN exome

AF:

0.118

Gnomad NFE exome

AF:

0.0519

Gnomad OTH exome

AF:

0.0453

GnomAD4 exome

AF:

0.0609

AC:

28132

AN:

461766

Hom.:

Cov.:

AF XY:

0.000591

AC XY:

AN XY:

93086

show subpopulations

Gnomad4 AFR exome

AF:

0.0545

Gnomad4 AMR exome

AF:

0.0311

Gnomad4 ASJ exome

AF:

0.0637

Gnomad4 EAS exome

AF:

0.0627

Gnomad4 SAS exome

AF:

0.0346

Gnomad4 FIN exome

AF:

0.0655

Gnomad4 NFE exome

AF:

0.0649

Gnomad4 OTH exome

AF:

0.0618

GnomAD4 genome

AF:

0.0122

AC:

1138

AN:

92992

Hom.:

Cov.:

AF XY:

0.00759

AC XY:

177

AN XY:

23320

show subpopulations

Gnomad4 AFR

AF:

0.0146

Gnomad4 AMR

AF:

0.0158

Gnomad4 ASJ

AF:

0.00388

Gnomad4 EAS

AF:

0.0159

Gnomad4 SAS

AF:

0.0206

Gnomad4 FIN

AF:

0.00949

Gnomad4 NFE

AF:

0.0103

Gnomad4 OTH

AF:

0.0189

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 21, 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

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