rs1863704

Variant names:

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.3008G>A(p.Gly1003Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 1,613,918 control chromosomes in the GnomAD database, including 108,220 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 7488 hom., cov: 32)

Exomes 𝑓: 0.36 ( 100732 hom. )

Consequence

STK36
NM_015690.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.900

Publications

62 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=0.0013133585).

BP6

Variant 2-218697952-G-A is Benign according to our data. Variant chr2-218697952-G-A is described in ClinVar as Benign. ClinVar VariationId is 403498.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK36	NM_015690.5 link	c.3008G>A	p.Gly1003Asp	missense_variant	Exon 25 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.3008G>A	p.Gly1003Asp	missense_variant	Exon 25 of 27	1	NM_015690.5	ENSP00000295709.3		Q9NRP7-1

Frequencies

GnomAD3 genomes

AF:

0.278

AC:

42250

AN:

151954

Hom.:

7488

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0695

Gnomad AMI

AF:

0.325

Gnomad AMR

AF:

0.334

Gnomad ASJ

AF:

0.351

Gnomad EAS

AF:

0.0616

Gnomad SAS

AF:

0.270

Gnomad FIN

AF:

0.399

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.387

Gnomad OTH

AF:

0.279

GnomAD2 exomes

AF:

0.319

AC:

80264

AN:

251388

AF XY:

0.325

show subpopulations

Gnomad AFR exome

AF:

0.0636

Gnomad AMR exome

AF:

0.341

Gnomad ASJ exome

AF:

0.343

Gnomad EAS exome

AF:

0.0606

Gnomad FIN exome

AF:

0.401

Gnomad NFE exome

AF:

0.382

Gnomad OTH exome

AF:

0.351

GnomAD4 exome

AF:

0.362

AC:

529721

AN:

1461846

Hom.:

100732

Cov.:

AF XY:

0.360

AC XY:

261769

AN XY:

727224

show subpopulations

African (AFR)

AF:

0.0591

AC:

1979

AN:

33480

American (AMR)

AF:

0.341

AC:

15238

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.346

AC:

9033

AN:

26136

East Asian (EAS)

AF:

0.0629

AC:

2496

AN:

39700

South Asian (SAS)

AF:

0.279

AC:

24099

AN:

86258

European-Finnish (FIN)

AF:

0.397

AC:

21198

AN:

53392

Middle Eastern (MID)

AF:

0.272

AC:

1569

AN:

5768

European-Non Finnish (NFE)

AF:

0.390

AC:

433912

AN:

1111992

Other (OTH)

AF:

0.334

AC:

20197

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

20170

40341

60511

80682

100852

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13302

26604

39906

53208

66510

<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:

0.278

AC:

42249

AN:

152072

Hom.:

7488

Cov.:

AF XY:

0.277

AC XY:

20556

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.0693

AC:

2879

AN:

41520

American (AMR)

AF:

0.333

AC:

5084

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.351

AC:

1219

AN:

3472

East Asian (EAS)

AF:

0.0622

AC:

322

AN:

5180

South Asian (SAS)

AF:

0.271

AC:

1307

AN:

4826

European-Finnish (FIN)

AF:

0.399

AC:

4209

AN:

10546

Middle Eastern (MID)

AF:

0.224

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.387

AC:

26276

AN:

67950

Other (OTH)

AF:

0.281

AC:

592

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1421

2841

4262

5682

7103

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

436

872

1308

1744

2180

<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:

0.344

Hom.:

33832

Bravo

AF:

0.266

TwinsUK

AF:

0.387

AC:

1434

ALSPAC

AF:

0.382

AC:

1473

ESP6500AA

AF:

0.0763

AC:

336

ESP6500EA

AF:

0.382

AC:

3284

ExAC

AF:

0.315

AC:

38187

Asia WGS

AF:

0.178

AC:

621

AN:

3478

EpiCase

AF:

0.380

EpiControl

AF:

0.378

ClinVar

Significance: Benign

Submissions summary: Benign:3

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

- -

Feb 06, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

0.13

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.31

CADD

Benign

9.7

(source)

DANN

Benign

0.28

DEOGEN2

Benign

0.12

T;.;T

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.064

LIST_S2

Benign

0.57

.;T;T

MetaRNN

Benign

0.0013

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

2.0

M;.;M

PhyloP100

0.90

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.45

N;N;N

REVEL

Benign

0.18

Sift

Benign

0.52

T;T;T

Sift4G

Benign

0.62

T;T;T

Polyphen

0.18

B;P;B

Vest4

0.085

MPC

0.22

ClinPred

0.0022

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.023

gMVP

0.45

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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