Variant 1-155263972-C-T 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_001294338.2(CLK2):c.1295G>A(p.Arg432His) variant causes a missense change. The variant allele was found at a frequency of 0.00025 in 1,614,118 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R432C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00096 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 1 hom. )

Consequence

CLK2
NM_001294338.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.17

Variant links:

Genes affected

CLK2 (HGNC:2069): (CDC like kinase 2) This gene encodes a dual specificity protein kinase that phosphorylates serine/threonine and tyrosine-containing substrates. Activity of this protein regulates serine- and arginine-rich (SR) proteins of the spliceosomal complex, thereby influencing alternative transcript splicing. Chromosomal translocations have been characterized between this locus and the PAFAH1B3 (platelet-activating factor acetylhydrolase 1b, catalytic subunit 3 (29kDa)) gene on chromosome 19, resulting in the production of a fusion protein. Note that this gene is distinct from the TELO2 gene (GeneID:9894), which shares the CLK2 alias, but encodes a protein that is involved in telomere length regulation. There is a pseudogene for this gene on chromosome 7. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

CLK2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.025280446).

BP6

Variant 1-155263972-C-T is Benign according to our data. Variant chr1-155263972-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 791812.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 146 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLK2	NM_001294338.2 link	c.1295G>A	p.Arg432His	missense_variant	12/13	ENST00000368361.9	NP_001281267.1	P49760-1A8K7I0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLK2	ENST00000368361.9 link	c.1295G>A	p.Arg432His	missense_variant	12/13	1	NM_001294338.2	ENSP00000357345.4		P49760-1

Frequencies

GnomAD3 genomes

AF:

0.000960

AC:

146

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00265

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:

0.00273

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000461

AC:

116

AN:

251482

Hom.:

AF XY:

0.000383

AC XY:

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.00344

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00231

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000176

AC:

258

AN:

1461864

Hom.:

Cov.:

AF XY:

0.000149

AC XY:

108

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00299

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00217

Gnomad4 NFE exome

AF:

0.0000144

Gnomad4 OTH exome

AF:

0.000281

GnomAD4 genome

AF:

0.000959

AC:

146

AN:

152254

Hom.:

Cov.:

AF XY:

0.000994

AC XY:

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.00265

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00273

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000154

Hom.:

Bravo

AF:

0.00104

ESP6500AA

AF:

0.00250

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000552

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.48

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.34

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.17

.;T;T

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Pathogenic

0.99

M_CAP

Benign

0.015

MetaRNN

Benign

0.025

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

.;M;.

PrimateAI

Pathogenic

0.85

PROVEAN

Uncertain

-4.3

D;D;D

REVEL

Uncertain

0.30

Sift

Uncertain

0.0020

D;D;D

Sift4G

Uncertain

0.0060

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.66

MVP

0.40

MPC

1.5

ClinPred

0.10

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.76

gMVP

0.60

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over