Variant X-18584219-ATTTC-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_001323289.2(CDKL5):c.464-40_464-37delCTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000737 in 884,973 control chromosomes in the GnomAD database, including 2 homozygotes. There are 183 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00058 ( 0 hom., 21 hem., cov: 23)

Exomes 𝑓: 0.00076 ( 2 hom. 162 hem. )

Consequence

CDKL5
NM_001323289.2 intron

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1O:1

Conservation

PhyloP100: 1.68

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 -9 ACMG points.

BP6

Variant X-18584219-ATTTC-A is Benign according to our data. Variant chrX-18584219-ATTTC-A is described in ClinVar as [Likely_benign]. Clinvar id is 156091.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000581 (65/111958) while in subpopulation NFE AF= 0.000828 (44/53163). AF 95% confidence interval is 0.000633. There are 0 homozygotes in gnomad4. There are 21 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 21 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
CDKL5	NM_001323289.2 linkuse as main transcript	c.464-40_464-37delCTTT	intron_variant	ENST00000623535.2	NP_001310218.1	O76039-2
CDKL5	NM_001037343.2 linkuse as main transcript	c.464-40_464-37delCTTT	intron_variant		NP_001032420.1	O76039-1
CDKL5	NM_003159.3 linkuse as main transcript	c.464-40_464-37delCTTT	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.464-40_464-37delCTTT		intron_variant		1	NM_001323289.2	ENSP00000485244.1		O76039-2

Frequencies

GnomAD3 genomes

AF:

0.000581

AC:

AN:

111905

Hom.:

Cov.:

AF XY:

0.000616

AC XY:

AN XY:

34097

show subpopulations

Gnomad AFR

AF:

0.0000649

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000285

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00248

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000828

Gnomad OTH

AF:

0.000661

GnomAD3 exomes

AF:

0.000712

AC:

130

AN:

182458

Hom.:

AF XY:

0.000521

AC XY:

AN XY:

67210

show subpopulations

Gnomad AFR exome

AF:

0.0000761

Gnomad AMR exome

AF:

0.000329

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00272

Gnomad NFE exome

AF:

0.000910

Gnomad OTH exome

AF:

0.000668

GnomAD4 exome

AF:

0.000759

AC:

587

AN:

773015

Hom.:

AF XY:

0.000730

AC XY:

162

AN XY:

222069

show subpopulations

Gnomad4 AFR exome

AF:

0.0000495

Gnomad4 AMR exome

AF:

0.000317

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00342

Gnomad4 NFE exome

AF:

0.000737

Gnomad4 OTH exome

AF:

0.000992

GnomAD4 genome

AF:

0.000581

AC:

AN:

111958

Hom.:

Cov.:

AF XY:

0.000615

AC XY:

AN XY:

34160

show subpopulations

Gnomad4 AFR

AF:

0.0000648

Gnomad4 AMR

AF:

0.000285

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00248

Gnomad4 NFE

AF:

0.000828

Gnomad4 OTH

AF:

0.000653

Alfa

AF:

0.000763

Hom.:

Bravo

AF:

0.000412

ClinVar

Significance: Likely benign

Submissions summary: Benign:1Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, no assertion criteria provided

curation

RettBASE

Mar 13, 2014

Unlikely to be pathogenic, not predicted to change splicing; however, there is no empirical evidence for this -

not provided

Other:1

not provided, flagged submission

literature only

RettBASE

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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