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

Variant summary

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

The NM_001323289.2(CDKL5):c.145+25_145+28dup variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., 1 hem., cov: 19)

Exomes 𝑓: 0.0013 ( 0 hom. 0 hem. )

Consequence

CDKL5
NM_001323289.2 splice_donor_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

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 Likely_benign. Variant got -6 ACMG points.

BP6

Variant X-18564526-G-GATAT is Benign according to our data. Variant chrX-18564526-G-GATAT is described in ClinVar as [Benign]. Clinvar id is 1169508.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000225 (21/93223) while in subpopulation AMR AF= 0.000361 (3/8316). AF 95% confidence interval is 0.000182. There are 0 homozygotes in gnomad4. There are 1 alleles in male gnomad4 subpopulation. Median coverage is 19. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
CDKL5	NM_001323289.2 linkuse as main transcript	c.145+25_145+28dup	splice_donor_region_variant, intron_variant	ENST00000623535.2	NP_001310218.1
CDKL5	NM_001037343.2 linkuse as main transcript	c.145+25_145+28dup	splice_donor_region_variant, intron_variant		NP_001032420.1
CDKL5	NM_003159.3 linkuse as main transcript	c.145+25_145+28dup	splice_donor_region_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+25_145+28dup		splice_donor_region_variant, intron_variant		1	NM_001323289.2	ENSP00000485244	P1	O76039-2

Frequencies

GnomAD3 genomes

AF:

0.000225

AC:

AN:

93248

Hom.:

Cov.:

AF XY:

0.0000427

AC XY:

AN XY:

23398

show subpopulations

Gnomad AFR

AF:

0.000350

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000361

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:

0.000172

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000798

AC:

AN:

72668

Hom.:

AF XY:

0.00

AC XY:

AN XY:

10808

show subpopulations

Gnomad AFR exome

AF:

0.000175

Gnomad AMR exome

AF:

0.000543

Gnomad ASJ exome

AF:

0.000901

Gnomad EAS exome

AF:

0.000706

Gnomad SAS exome

AF:

0.00120

Gnomad FIN exome

AF:

0.00130

Gnomad NFE exome

AF:

0.000867

Gnomad OTH exome

AF:

0.000509

GnomAD4 exome

AF:

0.00125

AC:

637

AN:

509058

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

123528

show subpopulations

Gnomad4 AFR exome

AF:

0.000827

Gnomad4 AMR exome

AF:

0.000925

Gnomad4 ASJ exome

AF:

0.00149

Gnomad4 EAS exome

AF:

0.000994

Gnomad4 SAS exome

AF:

0.000658

Gnomad4 FIN exome

AF:

0.000879

Gnomad4 NFE exome

AF:

0.00136

Gnomad4 OTH exome

AF:

0.00145

GnomAD4 genome

AF:

0.000225

AC:

AN:

93223

Hom.:

Cov.:

AF XY:

0.0000427

AC XY:

AN XY:

23399

show subpopulations

Gnomad4 AFR

AF:

0.000350

Gnomad4 AMR

AF:

0.000361

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000285

Gnomad4 NFE

AF:

0.000173

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

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 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