Variant chrX-18425831-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001323289.2(CDKL5):c.-163+136T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0131 in 112,405 control chromosomes in the GnomAD database, including 12 homozygotes. There are 413 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.013 ( 12 hom., 411 hem., cov: 24)

Exomes 𝑓: 0.015 ( 0 hom. 2 hem. )

Consequence

CDKL5
NM_001323289.2 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.262

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=-0.87).

BP6

Variant X-18425831-T-C is Benign according to our data. Variant chrX-18425831-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1189327.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0131 (1469/112271) while in subpopulation AFR AF= 0.0331 (1026/31002). AF 95% confidence interval is 0.0314. There are 12 homozygotes in gnomad4. There are 411 alleles in male gnomad4 subpopulation. Median coverage is 24. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 12 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDKL5	NM_001323289.2 linkuse as main transcript	c.-163+136T>C		intron_variant		ENST00000623535.2	NP_001310218.1	O76039-2
CDKL5	NM_003159.3 linkuse as main transcript	c.-163+136T>C		intron_variant			NP_003150.1	O76039-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
CDKL5	ENST00000623535.2 linkuse as main transcript	c.-163+136T>C	intron_variant	1	NM_001323289.2	ENSP00000485244.1	O76039-2
CDKL5	ENST00000379996.7 linkuse as main transcript	c.-163+136T>C	intron_variant	1		ENSP00000369332.3	O76039-1
CDKL5	ENST00000674046.1 linkuse as main transcript	c.-163+136T>C	intron_variant			ENSP00000501174.1	A0A669KBC2

Frequencies

GnomAD3 genomes

AF:

0.0131

AC:

1471

AN:

112229

Hom.:

Cov.:

AF XY:

0.0120

AC XY:

413

AN XY:

34517

show subpopulations

Gnomad AFR

AF:

0.0332

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00585

Gnomad ASJ

AF:

0.0295

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00363

Gnomad FIN

AF:

0.00368

Gnomad MID

AF:

0.0460

Gnomad NFE

AF:

0.00449

Gnomad OTH

AF:

0.0145

GnomAD4 exome

AF:

0.0149

AC:

AN:

134

Hom.:

AF XY:

0.0286

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00840

Gnomad4 OTH exome

AF:

0.143

GnomAD4 genome

AF:

0.0131

AC:

1469

AN:

112271

Hom.:

Cov.:

AF XY:

0.0119

AC XY:

411

AN XY:

34569

show subpopulations

Gnomad4 AFR

AF:

0.0331

Gnomad4 AMR

AF:

0.00584

Gnomad4 ASJ

AF:

0.0295

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00364

Gnomad4 FIN

AF:

0.00368

Gnomad4 NFE

AF:

0.00446

Gnomad4 OTH

AF:

0.0143

Alfa

AF:

0.00936

Hom.:

Bravo

AF:

0.0146

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 08, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

7.3

DANN

Benign

0.49

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