Variant chrX-18608991-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001323289.2(CDKL5):c.2046+79G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00937 in 672,225 control chromosomes in the GnomAD database, including 93 homozygotes. There are 1,789 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.021 ( 50 hom., 657 hem., cov: 22)

Exomes 𝑓: 0.0069 ( 43 hom. 1132 hem. )

Consequence

CDKL5
NM_001323289.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:2O:1

Conservation

PhyloP100: -3.65

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BP6

Variant X-18608991-G-A is Benign according to our data. Variant chrX-18608991-G-A is described in ClinVar as [Benign]. Clinvar id is 156076.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-18608991-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
CDKL5	NM_001323289.2 linkuse as main transcript	c.2046+79G>A	intron_variant	ENST00000623535.2	NP_001310218.1	O76039-2
CDKL5	NM_001037343.2 linkuse as main transcript	c.2046+79G>A	intron_variant		NP_001032420.1	O76039-1
CDKL5	NM_003159.3 linkuse as main transcript	c.2046+79G>A	intron_variant		NP_003150.1	O76039-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDKL5	ENST00000623535.2 linkuse as main transcript	c.2046+79G>A		intron_variant		1	NM_001323289.2	ENSP00000485244.1		O76039-2

Frequencies

GnomAD3 genomes

AF:

0.0215

AC:

2404

AN:

112034

Hom.:

Cov.:

AF XY:

0.0192

AC XY:

656

AN XY:

34246

show subpopulations

Gnomad AFR

AF:

0.0616

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00934

Gnomad ASJ

AF:

0.0302

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00444

Gnomad FIN

AF:

0.00347

Gnomad MID

AF:

0.0504

Gnomad NFE

AF:

0.00483

Gnomad OTH

AF:

0.0192

GnomAD4 exome

AF:

0.00695

AC:

3891

AN:

560138

Hom.:

AF XY:

0.00683

AC XY:

1132

AN XY:

165712

show subpopulations

Gnomad4 AFR exome

AF:

0.0584

Gnomad4 AMR exome

AF:

0.00703

Gnomad4 ASJ exome

AF:

0.0283

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00182

Gnomad4 FIN exome

AF:

0.00393

Gnomad4 NFE exome

AF:

0.00473

Gnomad4 OTH exome

AF:

0.0117

GnomAD4 genome

AF:

0.0215

AC:

2406

AN:

112087

Hom.:

Cov.:

AF XY:

0.0191

AC XY:

657

AN XY:

34309

show subpopulations

Gnomad4 AFR

AF:

0.0616

Gnomad4 AMR

AF:

0.00933

Gnomad4 ASJ

AF:

0.0302

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00445

Gnomad4 FIN

AF:

0.00347

Gnomad4 NFE

AF:

0.00479

Gnomad4 OTH

AF:

0.0190

Alfa

AF:

0.0143

Hom.:

Bravo

AF:

0.0240

ClinVar

Significance: Benign

Submissions summary: Benign:2Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, no assertion criteria provided

curation

RettBASE

Mar 13, 2014

- -

CDKL5 disorder

Benign:1

Benign, criteria provided, single submitter

curation

Centre for Population Genomics, CPG

Sep 16, 2024

This variant has been collected from RettBASE and curated to current modified ACMG/AMP criteria. Based on the classification scheme defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like Disorders Specifications to the ACMG/AMP Variant Interpretation Guidelines VCEP 3.0, this variant is classified as benign. At least the following criteria are met: The allele frequency of this variant in at least one population in gnomAD is higher than the 0.03% threshold defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like Disorders VCEP 3.0 (BA1). -

not provided

Other:1

not provided, flagged submission

literature only

RettBASE

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.0030

DANN

Benign

0.50

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