Genetic Variant CDKL5:c.-163+16798_-163+16817delTTTTGTTTTGTTTTGTTTTG (chrX-18442467-TTTTTGTTTTGTTTTGTTTTG-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001323289.2(CDKL5):c.-163+16798_-163+16817delTTTTGTTTTGTTTTGTTTTG variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000028 ( 0 hom., 0 hem., cov: 18)

Consequence

CDKL5
NM_001323289.2 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.942

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

CDKL5 disorder
Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
developmental and epileptic encephalopathy, 2
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
atypical Rett syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
genetic developmental and epileptic encephalopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
infantile spasms
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
precocious puberty
Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics

CDKL5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CDKL5	NM_001323289.2 link	c.-163+16798_-163+16817delTTTTGTTTTGTTTTGTTTTG	intron_variant	Intron 1 of 17	ENST00000623535.2	NP_001310218.1	O76039-2
CDKL5	NM_001037343.2 link	c.-163+70_-163+89delTTTTGTTTTGTTTTGTTTTG	intron_variant	Intron 2 of 21		NP_001032420.1	O76039-1
CDKL5	NM_003159.3 link	c.-163+16798_-163+16817delTTTTGTTTTGTTTTGTTTTG	intron_variant	Intron 1 of 20		NP_003150.1	O76039-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKL5	ENST00000623535.2 link	c.-163+16773_-163+16792delTTTTGTTTTGTTTTGTTTTG		intron_variant	Intron 1 of 17	1	NM_001323289.2	ENSP00000485244.1		O76039-2

Frequencies

GnomAD3 genomes

AF:

0.0000279

AC:

AN:

107445

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000344

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:

0.0000386

Gnomad OTH

AF:

0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0000279

AC:

AN:

107445

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

30729

show subpopulations

African (AFR)

AF:

0.0000344

AC:

AN:

29097

American (AMR)

AF:

0.00

AC:

AN:

10101

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2560

East Asian (EAS)

AF:

0.00

AC:

AN:

3425

South Asian (SAS)

AF:

0.00

AC:

AN:

2502

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5646

Middle Eastern (MID)

AF:

0.00

AC:

AN:

226

European-Non Finnish (NFE)

AF:

0.0000386

AC:

AN:

51800

Other (OTH)

AF:

0.00

AC:

AN:

1431

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

111

Bravo

AF:

0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.94

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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X-18442467-TTTTTGTTTTGTTTTGTTTTGTTTTG-TTTTTG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over