2-218690539-G-A

Position:

chr2-218690539-G-A

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. 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:2

Conservation

PhyloP100: 1.78

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
STK36	NM_015690.5 linkuse as main transcript	c.1748G>A	p.Arg583Gln	missense_variant	14/27	ENST00000295709.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK36	ENST00000295709.8 linkuse as main transcript	c.1748G>A	p.Arg583Gln	missense_variant	14/27	1	NM_015690.5	P1	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

GnomAD3 exomes

AF:

0.413

AC:

103838

AN:

251210

Hom.:

22959

AF XY:

0.409

AC XY:

55487

AN XY:

135778

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 SAS exome

AF:

0.337

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

Gnomad4 AFR exome

AF:

0.658

Gnomad4 AMR exome

AF:

0.406

Gnomad4 ASJ exome

AF:

0.410

Gnomad4 EAS exome

AF:

0.129

Gnomad4 SAS exome

AF:

0.337

Gnomad4 FIN exome

AF:

0.441

Gnomad4 NFE exome

AF:

0.445

Gnomad4 OTH exome

AF:

0.434

GnomAD4 genome

AF:

0.483

AC:

73359

AN:

152020

Hom.:

18802

Cov.:

AF XY:

0.475

AC XY:

35284

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.644

Gnomad4 AMR

AF:

0.443

Gnomad4 ASJ

AF:

0.415

Gnomad4 EAS

AF:

0.139

Gnomad4 SAS

AF:

0.328

Gnomad4 FIN

AF:

0.437

Gnomad4 NFE

AF:

0.444

Gnomad4 OTH

AF:

0.457

Alfa

AF:

0.438

Hom.:

36217

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

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 -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 04, 2021

- -

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

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

MutationTaster

Benign

1.0

P;P;P;P

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

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

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