rs1344642

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_015690.5(STK36):c.1748G>A(p.Arg583Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 1,612,946 control chromosomes in the GnomAD database, including 159,073 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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. R583W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.48 ( 18802 hom., cov: 32)

Exomes 𝑓: 0.43 ( 140271 hom. )

Consequence

STK36
NM_015690.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.78

Publications

60 publications found

Variant links:

Genes affected

STK36 (HGNC:17209): (serine/threonine kinase 36) This gene encodes a member of the serine/threonine kinase family of enzymes. This family member is similar to a Drosophila protein that plays a key role in the Hedgehog signaling pathway. This human protein is a positive regulator of the GLI zinc-finger transcription factors. Knockout studies of the homologous mouse gene suggest that defects in this human gene may lead to congenital hydrocephalus, possibly due to a functional defect in motile cilia. Because Hedgehog signaling is frequently activated in certain kinds of gastrointestinal cancers, it has been suggested that this gene is a target for the treatment of these cancers. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Aug 2011]

STK36 Gene-Disease associations (from GenCC):

primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
ciliary dyskinesia, primary, 46
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

STK36 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=3.5153664E-6).

BP6

Variant 2-218690539-G-A is Benign according to our data. Variant chr2-218690539-G-A is described in ClinVar as Benign. ClinVar VariationId is 403497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK36	NM_015690.5 link	c.1748G>A	p.Arg583Gln	missense_variant	Exon 14 of 27	ENST00000295709.8	NP_056505.2	Q9NRP7-1A0A140VJW1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK36	ENST00000295709.8 link	c.1748G>A	p.Arg583Gln	missense_variant	Exon 14 of 27	1	NM_015690.5	ENSP00000295709.3		Q9NRP7-1

Frequencies

GnomAD3 genomes

AF:

0.482

AC:

73247

AN:

151902

Hom.:

18751

Cov.:

show subpopulations

Gnomad AFR

AF:

0.643

Gnomad AMI

AF:

0.350

Gnomad AMR

AF:

0.443

Gnomad ASJ

AF:

0.415

Gnomad EAS

AF:

0.138

Gnomad SAS

AF:

0.327

Gnomad FIN

AF:

0.437

Gnomad MID

AF:

0.404

Gnomad NFE

AF:

0.444

Gnomad OTH

AF:

0.457

GnomAD2 exomes

AF:

0.413

AC:

103838

AN:

251210

AF XY:

0.409

show subpopulations

Gnomad AFR exome

AF:

0.653

Gnomad AMR exome

AF:

0.402

Gnomad ASJ exome

AF:

0.405

Gnomad EAS exome

AF:

0.137

Gnomad FIN exome

AF:

0.445

Gnomad NFE exome

AF:

0.441

Gnomad OTH exome

AF:

0.434

GnomAD4 exome

AF:

0.432

AC:

631525

AN:

1460926

Hom.:

140271

Cov.:

AF XY:

0.428

AC XY:

311188

AN XY:

726824

show subpopulations

African (AFR)

AF:

0.658

AC:

22023

AN:

33460

American (AMR)

AF:

0.406

AC:

18140

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.410

AC:

10717

AN:

26128

East Asian (EAS)

AF:

0.129

AC:

5125

AN:

39688

South Asian (SAS)

AF:

0.337

AC:

29036

AN:

86236

European-Finnish (FIN)

AF:

0.441

AC:

23576

AN:

53414

Middle Eastern (MID)

AF:

0.387

AC:

2231

AN:

5764

European-Non Finnish (NFE)

AF:

0.445

AC:

494511

AN:

1111172

Other (OTH)

AF:

0.434

AC:

26166

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

16637

33275

49912

66550

83187

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14878

29756

44634

59512

74390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.483

AC:

73359

AN:

152020

Hom.:

18802

Cov.:

AF XY:

0.475

AC XY:

35284

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.644

AC:

26695

AN:

41446

American (AMR)

AF:

0.443

AC:

6754

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.415

AC:

1439

AN:

3470

East Asian (EAS)

AF:

0.139

AC:

717

AN:

5164

South Asian (SAS)

AF:

0.328

AC:

1579

AN:

4816

European-Finnish (FIN)

AF:

0.437

AC:

4620

AN:

10566

Middle Eastern (MID)

AF:

0.408

AC:

119

AN:

292

European-Non Finnish (NFE)

AF:

0.444

AC:

30151

AN:

67984

Other (OTH)

AF:

0.457

AC:

966

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1856

3712

5567

7423

9279

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

648

1296

1944

2592

3240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.447

Hom.:

52976

Bravo

AF:

0.492

TwinsUK

AF:

0.444

AC:

1645

ALSPAC

AF:

0.445

AC:

1714

ESP6500AA

AF:

0.636

AC:

2804

ESP6500EA

AF:

0.439

AC:

3775

ExAC

AF:

0.419

AC:

50909

Asia WGS

AF:

0.281

AC:

980

AN:

3478

EpiCase

AF:

0.442

EpiControl

AF:

0.444

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.13

T;.;T

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.77

.;T;T

MetaRNN

Benign

0.0000035

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.26

N;N;N

PhyloP100

1.8

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.74

N;N;N

REVEL

Benign

0.025

Sift

Benign

0.13

T;T;T

Sift4G

Benign

0.54

T;T;T

Polyphen

0.041

B;B;B

Vest4

0.087

MPC

0.20

ClinPred

0.0017

GERP RS

2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.039

gMVP

0.31

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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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