rs1863703

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.884A>G(p.Lys295Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.071 in 1,614,022 control chromosomes in the GnomAD database, including 7,694 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 0.14 ( 2851 hom., cov: 32)

Exomes 𝑓: 0.064 ( 4843 hom. )

Consequence

STK36
NM_015690.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.88

Publications

27 publications found

Variant links:

COSMIC-nc: COSV99831077

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=0.0037926435).

BP6

Variant 2-218679665-A-G is Benign according to our data. Variant chr2-218679665-A-G is described in ClinVar as [Benign]. Clinvar id is 1280618.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK36	NM_015690.5 link	c.884A>G	p.Lys295Arg	missense_variant	Exon 8 of 27	ENST00000295709.8	NP_056505.2	Q9NRP7-1A0A140VJW1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
STK36	ENST00000295709.8 link	c.884A>G	p.Lys295Arg	missense_variant	Exon 8 of 27	1	NM_015690.5	ENSP00000295709.3	Q9NRP7-1
STK36	ENST00000392105.7 link	c.884A>G	p.Lys295Arg	missense_variant	Exon 8 of 27	1		ENSP00000375954.3	Q9NRP7-2
STK36	ENST00000440309.5 link	c.884A>G	p.Lys295Arg	missense_variant	Exon 8 of 27	5		ENSP00000394095.1	Q9NRP7-1
STK36	ENST00000424080.1 link	c.*48A>G		downstream_gene_variant		5		ENSP00000403527.1	C9JDA4

Frequencies

GnomAD3 genomes

AF:

0.141

AC:

21481

AN:

152018

Hom.:

2839

Cov.:

show subpopulations

Gnomad AFR

AF:

0.357

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.0838

Gnomad ASJ

AF:

0.0634

Gnomad EAS

AF:

0.0764

Gnomad SAS

AF:

0.0552

Gnomad FIN

AF:

0.0374

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.0561

Gnomad OTH

AF:

0.136

GnomAD2 exomes

AF:

0.0779

AC:

19566

AN:

251286

AF XY:

0.0723

show subpopulations

Gnomad AFR exome

AF:

0.369

Gnomad AMR exome

AF:

0.0510

Gnomad ASJ exome

AF:

0.0617

Gnomad EAS exome

AF:

0.0769

Gnomad FIN exome

AF:

0.0443

Gnomad NFE exome

AF:

0.0583

Gnomad OTH exome

AF:

0.0763

GnomAD4 exome

AF:

0.0636

AC:

93010

AN:

1461886

Hom.:

4843

Cov.:

AF XY:

0.0628

AC XY:

45665

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.377

AC:

12636

AN:

33480

American (AMR)

AF:

0.0534

AC:

2388

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0646

AC:

1689

AN:

26136

East Asian (EAS)

AF:

0.0664

AC:

2637

AN:

39700

South Asian (SAS)

AF:

0.0566

AC:

4882

AN:

86258

European-Finnish (FIN)

AF:

0.0444

AC:

2372

AN:

53418

Middle Eastern (MID)

AF:

0.103

AC:

593

AN:

5768

European-Non Finnish (NFE)

AF:

0.0546

AC:

60724

AN:

1112008

Other (OTH)

AF:

0.0843

AC:

5089

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

5259

10518

15778

21037

26296

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.142

AC:

21544

AN:

152136

Hom.:

2851

Cov.:

AF XY:

0.137

AC XY:

10160

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.357

AC:

14808

AN:

41436

American (AMR)

AF:

0.0838

AC:

1281

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0634

AC:

220

AN:

3470

East Asian (EAS)

AF:

0.0766

AC:

396

AN:

5170

South Asian (SAS)

AF:

0.0557

AC:

269

AN:

4832

European-Finnish (FIN)

AF:

0.0374

AC:

397

AN:

10614

Middle Eastern (MID)

AF:

0.163

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0561

AC:

3815

AN:

68012

Other (OTH)

AF:

0.136

AC:

286

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

809

1618

2427

3236

4045

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0829

Hom.:

3374

Bravo

AF:

0.155

TwinsUK

AF:

0.0566

AC:

210

ALSPAC

AF:

0.0618

AC:

238

ESP6500AA

AF:

0.351

AC:

1548

ESP6500EA

AF:

0.0565

AC:

486

ExAC

AF:

0.0847

AC:

10282

Asia WGS

AF:

0.0860

AC:

297

AN:

3478

EpiCase

AF:

0.0620

EpiControl

AF:

0.0649

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

- -

May 05, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.10

T;.;T

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.78

.;T;T

MetaRNN

Benign

0.0038

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.9

L;L;L

PhyloP100

1.9

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.18

N;N;N

REVEL

Benign

0.035

Sift

Benign

0.44

T;T;T

Sift4G

Benign

0.66

T;T;T

Polyphen

0.056

B;B;B

Vest4

0.066

MPC

0.14

ClinPred

0.014

GERP RS

3.0

Varity_R

0.029

gMVP

0.24

Mutation Taster

=99/1

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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rs1863703

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