Variant 2-218672514-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015690.5(STK36):c.-89-227A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.047 in 362,324 control chromosomes in the GnomAD database, including 588 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.056 ( 327 hom., cov: 32)

Exomes 𝑓: 0.041 ( 261 hom. )

Consequence

STK36
NM_015690.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.529

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 2-218672514-A-T is Benign according to our data. Variant chr2-218672514-A-T is described in ClinVar as [Benign]. Clinvar id is 1279043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK36	NM_015690.5 linkuse as main transcript	c.-89-227A>T		intron_variant		ENST00000295709.8	NP_056505.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK36	ENST00000295709.8 linkuse as main transcript	c.-89-227A>T		intron_variant		1	NM_015690.5	ENSP00000295709	P1	Q9NRP7-1

Frequencies

GnomAD3 genomes

AF:

0.0556

AC:

8441

AN:

151870

Hom.:

326

Cov.:

show subpopulations

Gnomad AFR

AF:

0.103

Gnomad AMI

AF:

0.0220

Gnomad AMR

AF:

0.0311

Gnomad ASJ

AF:

0.0337

Gnomad EAS

AF:

0.119

Gnomad SAS

AF:

0.0441

Gnomad FIN

AF:

0.0289

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0339

Gnomad OTH

AF:

0.0513

GnomAD4 exome

AF:

0.0408

AC:

8586

AN:

210336

Hom.:

261

AF XY:

0.0408

AC XY:

4630

AN XY:

113476

show subpopulations

Gnomad4 AFR exome

AF:

0.0995

Gnomad4 AMR exome

AF:

0.0254

Gnomad4 ASJ exome

AF:

0.0352

Gnomad4 EAS exome

AF:

0.113

Gnomad4 SAS exome

AF:

0.0420

Gnomad4 FIN exome

AF:

0.0393

Gnomad4 NFE exome

AF:

0.0332

Gnomad4 OTH exome

AF:

0.0382

GnomAD4 genome

AF:

0.0556

AC:

8454

AN:

151988

Hom.:

327

Cov.:

AF XY:

0.0546

AC XY:

4056

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.103

Gnomad4 AMR

AF:

0.0312

Gnomad4 ASJ

AF:

0.0337

Gnomad4 EAS

AF:

0.120

Gnomad4 SAS

AF:

0.0441

Gnomad4 FIN

AF:

0.0289

Gnomad4 NFE

AF:

0.0339

Gnomad4 OTH

AF:

0.0508

Alfa

AF:

0.0455

Hom.:

Bravo

AF:

0.0582

Asia WGS

AF:

0.0690

AC:

238

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 16, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

3.1

DANN

Benign

0.71

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