chr2-218680586-T-C

Variant names:

• chr2-218680586-T-C
• rs2303565
• NM_015690.5:c.1137-17T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015690.5(STK36):​c.1137-17T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 1,603,632 control chromosomes in the GnomAD database, including 171,418 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.54 (25604 hom., cov: 31)
  • Exomes 𝑓: 0.44 (145814 hom.)
• Consequence: STK36 NM_015690.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.00
• Publications: 36 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 2-218680586-T-C is Benign according to our data. Variant chr2-218680586-T-C is described in ClinVar as Benign. ClinVar VariationId is 1265137.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK36	NM_015690.5	c.1137-17T>C		intron_variant	Intron 9 of 26	ENST00000295709.8	NP_056505.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK36	ENST00000295709.8	c.1137-17T>C		intron_variant	Intron 9 of 26	1	NM_015690.5	ENSP00000295709.3

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82513 AN: 151898 Hom.: 25539 Cov.: 31

Gnomad AFR AF: 0.854

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.436

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.506

GnomAD2 exomes AF: 0.425 AC: 100411 AN: 236130 AF XY: 0.417

Gnomad AFR exome AF: 0.864

Gnomad AMR exome AF: 0.410

Gnomad ASJ exome AF: 0.405

Gnomad EAS exome AF: 0.136

Gnomad FIN exome AF: 0.443

Gnomad NFE exome AF: 0.439

Gnomad OTH exome AF: 0.441

GnomAD4 exome AF: 0.439 AC: 636921 AN: 1451616 Hom.: 145814 Cov.: 30 AF XY: 0.434 AC XY: 312860 AN XY: 721228

African (AFR) AF: 0.875 AC: 29189 AN: 33364

American (AMR) AF: 0.416 AC: 18049 AN: 43410

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 10639 AN: 25932

East Asian (EAS) AF: 0.129 AC: 5100 AN: 39506

South Asian (SAS) AF: 0.337 AC: 28432 AN: 84390

European-Finnish (FIN) AF: 0.441 AC: 23231 AN: 52716

Middle Eastern (MID) AF: 0.395 AC: 2274 AN: 5754

European-Non Finnish (NFE) AF: 0.446 AC: 493104 AN: 1106540

Other (OTH) AF: 0.448 AC: 26903 AN: 60004

GnomAD4 genome AF: 0.544 AC: 82637 AN: 152016 Hom.: 25604 Cov.: 31 AF XY: 0.535 AC XY: 39726 AN XY: 74302

African (AFR) AF: 0.854 AC: 35454 AN: 41496

American (AMR) AF: 0.465 AC: 7097 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 1435 AN: 3468

East Asian (EAS) AF: 0.138 AC: 716 AN: 5170

South Asian (SAS) AF: 0.328 AC: 1580 AN: 4814

European-Finnish (FIN) AF: 0.436 AC: 4601 AN: 10550

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.445 AC: 30216 AN: 67942

Other (OTH) AF: 0.505 AC: 1066 AN: 2110

Alfa AF: 0.499 Hom.: 23818

Bravo AF: 0.561

Asia WGS AF: 0.293 AC: 1023 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 15, 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
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.1
DANN	Benign	0.69
PhyloP100		-2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2303565; hg19: chr2-219545309; COSMIC: COSV55325126; COSMIC: COSV55325126;