Variant X-18604655-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001323289.2(CDKL5):c.1731G>T(p.Met577Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,635 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

CDKL5
NM_001323289.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.34

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08585766).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDKL5	NM_001323289.2 linkuse as main transcript	c.1731G>T	p.Met577Ile	missense_variant	12/18	ENST00000623535.2	NP_001310218.1	O76039-2
CDKL5	NM_001037343.2 linkuse as main transcript	c.1731G>T	p.Met577Ile	missense_variant	13/22		NP_001032420.1	O76039-1
CDKL5	NM_003159.3 linkuse as main transcript	c.1731G>T	p.Met577Ile	missense_variant	12/21		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.1731G>T	p.Met577Ile	missense_variant	12/18	1	NM_001323289.2	ENSP00000485244.1		O76039-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000546

AC:

AN:

183233

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67701

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

9.11e-7

AC:

AN:

1097635

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

362999

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.030

T;T;T;.;.

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.78

.;T;T;T;T

M_CAP

Benign

0.040

MetaRNN

Benign

0.086

T;T;T;T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

0.69

N;.;N;.;N

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.72

N;.;N;.;.

REVEL

Benign

0.16

Sift

Uncertain

0.0090

D;.;D;.;.

Sift4G

Benign

0.16

T;.;T;T;T

Polyphen

0.0

B;.;B;.;.

Vest4

0.17

MutPred

0.049

Gain of glycosylation at S580 (P = 0.0828);Gain of glycosylation at S580 (P = 0.0828);Gain of glycosylation at S580 (P = 0.0828);Gain of glycosylation at S580 (P = 0.0828);Gain of glycosylation at S580 (P = 0.0828);

MVP

0.49

MPC

0.38

ClinPred

0.11

GERP RS

4.2

Varity_R

0.39

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over