rs17853159

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_007170.3(TESK2):c.1363C>T(p.Arg455Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0682 in 1,614,134 control chromosomes in the GnomAD database, including 4,320 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R455H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.050 ( 274 hom., cov: 32)

Exomes 𝑓: 0.070 ( 4046 hom. )

Consequence

TESK2
NM_007170.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.28

Publications

20 publications found

Variant links:

Genes affected

TESK2 (HGNC:11732): (testis associated actin remodelling kinase 2) This gene product is a serine/threonine protein kinase that contains an N-terminal protein kinase domain that is structurally similar to the kinase domains of testis-specific protein kinase-1 and the LIM motif-containing protein kinases (LIMKs). Its overall structure is most related to the former, indicating that it belongs to the TESK subgroup of the LIMK/TESK family of protein kinases. This gene is predominantly expressed in testis and prostate. The developmental expression pattern of the rat gene in testis suggests an important role for this gene in meitoic stages and/or early stages of spermiogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

TESK2 links:

ENSG00000288208 (HGNC:):

ENSG00000288208 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0024671257).

BP6

Variant 1-45345193-G-A is Benign according to our data. Variant chr1-45345193-G-A is described in ClinVar as [Benign]. Clinvar id is 1264064.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TESK2	NM_007170.3 link	c.1363C>T	p.Arg455Cys	missense_variant	Exon 11 of 11	ENST00000372086.4	NP_009101.2	Q96S53-1
TESK2	NM_001320800.2 link	c.1114C>T	p.Arg372Cys	missense_variant	Exon 10 of 10		NP_001307729.1	Q96S53B4DFN2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TESK2	ENST00000372086.4 link	c.1363C>T	p.Arg455Cys	missense_variant	Exon 11 of 11	1	NM_007170.3	ENSP00000361158.3	Q96S53-1
TESK2	ENST00000372084.5 link	c.1276C>T	p.Arg426Cys	missense_variant	Exon 9 of 9	1		ENSP00000361156.1	Q96S53-3
ENSG00000288208	ENST00000671898.1 link	n.540+10110C>T		intron_variant	Intron 5 of 20			ENSP00000499896.1	A0A5F9ZGZ0
TESK2	ENST00000486676.5 link	n.1710C>T		non_coding_transcript_exon_variant	Exon 10 of 10	5

Frequencies

GnomAD3 genomes

AF:

0.0501

AC:

7618

AN:

152180

Hom.:

274

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0120

Gnomad AMI

AF:

0.0385

Gnomad AMR

AF:

0.0344

Gnomad ASJ

AF:

0.0418

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0317

Gnomad FIN

AF:

0.0768

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0786

Gnomad OTH

AF:

0.0421

GnomAD2 exomes

AF:

0.0517

AC:

12899

AN:

249306

AF XY:

0.0527

show subpopulations

Gnomad AFR exome

AF:

0.0114

Gnomad AMR exome

AF:

0.0203

Gnomad ASJ exome

AF:

0.0432

Gnomad EAS exome

AF:

0.000222

Gnomad FIN exome

AF:

0.0767

Gnomad NFE exome

AF:

0.0760

Gnomad OTH exome

AF:

0.0537

GnomAD4 exome

AF:

0.0701

AC:

102537

AN:

1461836

Hom.:

4046

Cov.:

AF XY:

0.0693

AC XY:

50372

AN XY:

727226

show subpopulations

African (AFR)

AF:

0.0106

AC:

355

AN:

33478

American (AMR)

AF:

0.0224

AC:

1003

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0429

AC:

1121

AN:

26134

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.0341

AC:

2944

AN:

86258

European-Finnish (FIN)

AF:

0.0766

AC:

4089

AN:

53370

Middle Eastern (MID)

AF:

0.0196

AC:

113

AN:

5768

European-Non Finnish (NFE)

AF:

0.0801

AC:

89032

AN:

1112010

Other (OTH)

AF:

0.0642

AC:

3878

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

6243

12486

18729

24972

31215

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0500

AC:

7618

AN:

152298

Hom.:

274

Cov.:

AF XY:

0.0491

AC XY:

3653

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.0120

AC:

499

AN:

41574

American (AMR)

AF:

0.0343

AC:

525

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0418

AC:

145

AN:

3472

East Asian (EAS)

AF:

0.000578

AC:

AN:

5188

South Asian (SAS)

AF:

0.0315

AC:

152

AN:

4826

European-Finnish (FIN)

AF:

0.0768

AC:

814

AN:

10604

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0787

AC:

5350

AN:

68016

Other (OTH)

AF:

0.0416

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

382

764

1146

1528

1910

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0644

Hom.:

808

Bravo

AF:

0.0459

TwinsUK

AF:

0.0777

AC:

288

ALSPAC

AF:

0.0859

AC:

331

ESP6500AA

AF:

0.0135

AC:

ESP6500EA

AF:

0.0731

AC:

602

ExAC

AF:

0.0522

AC:

6311

Asia WGS

AF:

0.0190

AC:

AN:

3478

EpiCase

AF:

0.0710

EpiControl

AF:

0.0690

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 11, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 28379579) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.14

.;T

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.31

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.84

T;D

MetaRNN

Benign

0.0025

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.1

.;L

PhyloP100

4.3

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-3.5

D;D

REVEL

Uncertain

0.29

Sift

Benign

0.053

T;T

Sift4G

Uncertain

0.035

D;D

Polyphen

0.030

B;B

Vest4

0.070

MPC

0.28

ClinPred

0.025

GERP RS

4.0

Varity_R

0.14

gMVP

0.40

Mutation Taster

=95/5

polymorphism (auto)

(source)

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

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rs17853159

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over