Variant rs374030184 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001323289.2(CDKL5):c.464-9A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000747 in 1,164,119 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 26 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., 5 hem., cov: 23)

Exomes 𝑓: 0.000069 ( 0 hom. 21 hem. )

Consequence

CDKL5
NM_001323289.2 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.000006842

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.911

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant X-18584254-A-G is Benign according to our data. Variant chrX-18584254-A-G is described in ClinVar as [Benign]. Clinvar id is 533399.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-18584254-A-G is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd4 at 5 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
CDKL5	NM_001323289.2 linkuse as main transcript	c.464-9A>G	splice_polypyrimidine_tract_variant, intron_variant	ENST00000623535.2	NP_001310218.1
CDKL5	NM_001037343.2 linkuse as main transcript	c.464-9A>G	splice_polypyrimidine_tract_variant, intron_variant		NP_001032420.1
CDKL5	NM_003159.3 linkuse as main transcript	c.464-9A>G	splice_polypyrimidine_tract_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.464-9A>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001323289.2	ENSP00000485244	P1	O76039-2

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

111945

Hom.:

Cov.:

AF XY:

0.000147

AC XY:

AN XY:

34123

show subpopulations

Gnomad AFR

AF:

0.000162

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000169

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000983

AC:

AN:

183096

Hom.:

AF XY:

0.000118

AC XY:

AN XY:

67688

show subpopulations

Gnomad AFR exome

AF:

0.000228

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000524

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000159

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000694

AC:

AN:

1052174

Hom.:

Cov.:

AF XY:

0.0000641

AC XY:

AN XY:

327536

show subpopulations

Gnomad4 AFR exome

AF:

0.0000783

Gnomad4 AMR exome

AF:

0.0000285

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000666

Gnomad4 SAS exome

AF:

0.0000565

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000762

Gnomad4 OTH exome

AF:

0.0000674

GnomAD4 genome

AF:

0.000125

AC:

AN:

111945

Hom.:

Cov.:

AF XY:

0.000147

AC XY:

AN XY:

34123

show subpopulations

Gnomad4 AFR

AF:

0.000162

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000169

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000182

Hom.:

Bravo

AF:

0.000166

EpiCase

AF:

0.000218

EpiControl

AF:

0.000475

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 15, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.0090

DANN

Benign

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0000068

dbscSNV1_RF

Benign

0.0060

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