rs55839518

Variant names:

• chr2-218680624-T-C
• rs55839518
• NM_015690.5:c.1158T>C

Your query was ambiguous. Multiple possible variants found:

• chr2-218680624-T-C
• chr2-218680624-T-G

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_015690.5(STK36):​c.1158T>C​(p.Asp386Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00441 in 1,613,450 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0034 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0045 (17 hom.)
• Consequence: STK36 NM_015690.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.32
• Publications: 1 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):

• ciliary dyskinesia, primary, 46

  Inheritance: AR Classification: MODERATE, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 2-218680624-T-C is Benign according to our data. Variant chr2-218680624-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 403499.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.32 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 3 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015690.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK36	NM_015690.5	MANE Select	c.1158T>C	p.Asp386Asp	synonymous	Exon 10 of 27	NP_056505.2	Q9NRP7-1
	STK36	NM_001369423.1		c.1158T>C	p.Asp386Asp	synonymous	Exon 10 of 27	NP_001356352.1	Q9NRP7-1
	STK36	NM_001243313.2		c.1158T>C	p.Asp386Asp	synonymous	Exon 10 of 27	NP_001230242.1	Q9NRP7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK36	ENST00000295709.8	TSL:1 MANE Select	c.1158T>C	p.Asp386Asp	synonymous	Exon 10 of 27	ENSP00000295709.3	Q9NRP7-1
	STK36	ENST00000392105.7	TSL:1	c.1158T>C	p.Asp386Asp	synonymous	Exon 10 of 27	ENSP00000375954.3	Q9NRP7-2
	STK36	ENST00000440309.5	TSL:5	c.1158T>C	p.Asp386Asp	synonymous	Exon 10 of 27	ENSP00000394095.1	Q9NRP7-1

Frequencies

GnomAD3 genomes AF: 0.00342 AC: 521 AN: 152192 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00101

Gnomad AMI AF: 0.00659

Gnomad AMR AF: 0.00393

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.000941

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00557

Gnomad OTH AF: 0.00669

GnomAD2 exomes AF: 0.00334 AC: 833 AN: 249402 AF XY: 0.00343

Gnomad AFR exome AF: 0.000623

Gnomad AMR exome AF: 0.00334

Gnomad ASJ exome AF: 0.00210

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.00136

Gnomad NFE exome AF: 0.00548

Gnomad OTH exome AF: 0.00412

GnomAD4 exome AF: 0.00451 AC: 6594 AN: 1461140 Hom.: 17 Cov.: 31 AF XY: 0.00450 AC XY: 3267 AN XY: 726776

African (AFR) AF: 0.00102 AC: 34 AN: 33470

American (AMR) AF: 0.00360 AC: 161 AN: 44668

Ashkenazi Jewish (ASJ) AF: 0.00184 AC: 48 AN: 26092

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.000488 AC: 42 AN: 85982

European-Finnish (FIN) AF: 0.00182 AC: 97 AN: 53316

Middle Eastern (MID) AF: 0.00347 AC: 20 AN: 5768

European-Non Finnish (NFE) AF: 0.00533 AC: 5922 AN: 1111800

Other (OTH) AF: 0.00447 AC: 270 AN: 60356

GnomAD4 genome AF: 0.00342 AC: 521 AN: 152310 Hom.: 3 Cov.: 32 AF XY: 0.00302 AC XY: 225 AN XY: 74482

African (AFR) AF: 0.00101 AC: 42 AN: 41570

American (AMR) AF: 0.00392 AC: 60 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4828

European-Finnish (FIN) AF: 0.000941 AC: 10 AN: 10626

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00557 AC: 379 AN: 68024

Other (OTH) AF: 0.00662 AC: 14 AN: 2114

Alfa AF: 0.00395 Hom.: 1

Bravo AF: 0.00368

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00742

EpiControl AF: 0.00629

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)
-	-	1	STK36-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.32
DANN	Benign	0.33
PhyloP100		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs55839518; hg19: chr2-219545347;