Variant 4-75597232-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_001330724.2(CDKL2):c.1025C>A(p.Thr342Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000281 in 1,424,308 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

CDKL2
NM_001330724.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.99

Variant links:

Genes affected

CDKL2 (HGNC:1782): (cyclin dependent kinase like 2) This gene product is a member of a large family of CDC2-related serine/threonine protein kinases. It accumulates primarily in the cytoplasm, with lower levels in the nucleus. [provided by RefSeq, Jul 2008]

CDKL2 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=0.12404281).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDKL2	NM_001330724.2 linkuse as main transcript	c.1025C>A	p.Thr342Asn	missense_variant	9/14	ENST00000307465.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDKL2	ENST00000307465.9 linkuse as main transcript	c.1025C>A	p.Thr342Asn	missense_variant	9/14	2	NM_001330724.2	P1
CDKL2	ENST00000429927.6 linkuse as main transcript	c.1025C>A	p.Thr342Asn	missense_variant	9/12	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000406

AC:

AN:

246016

Hom.:

AF XY:

0.00000748

AC XY:

AN XY:

133614

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000894

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000281

AC:

AN:

1424308

Hom.:

Cov.:

AF XY:

0.00000282

AC XY:

AN XY:

709832

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000277

Gnomad4 OTH exome

AF:

0.0000170

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 07, 2023

The c.1025C>A (p.T342N) alteration is located in exon 9 (coding exon 8) of the CDKL2 gene. This alteration results from a C to A substitution at nucleotide position 1025, causing the threonine (T) at amino acid position 342 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.081

T;.

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.81

T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

M;.

MutationTaster

Benign

0.99

N;N

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.65

N;N

REVEL

Benign

0.056

Sift

Benign

0.21

T;T

Sift4G

Benign

0.16

T;T

Polyphen

0.17

B;.

Vest4

0.15

MutPred

0.14

Loss of phosphorylation at T342 (P = 0.0591);Loss of phosphorylation at T342 (P = 0.0591);

MVP

0.62

MPC

0.018

ClinPred

0.17

GERP RS

2.8

Varity_R

0.063

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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