rs2241527

Variant names:

• chr2-218672501-G-A
• rs2241527
• NM_015690.5:c.-89-240G>A

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.-89-240G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 343,894 control chromosomes in the GnomAD database, including 18,901 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (7498 hom., cov: 31)
  • Exomes 𝑓: 0.33 (11403 hom.)
• Consequence: STK36 NM_015690.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.177
• Publications: 14 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: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, PanelApp Australia
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 2-218672501-G-A is Benign according to our data. Variant chr2-218672501-G-A is described in ClinVar as Benign. ClinVar VariationId is 1229044.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

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.-89-240G>A		intron	N/A	NP_056505.2	Q9NRP7-1
	STK36	NM_001369423.1		c.-90+136G>A		intron	N/A	NP_001356352.1	Q9NRP7-1
	STK36	NM_001243313.2		c.-89-240G>A		intron	N/A	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.-89-240G>A		intron	N/A	ENSP00000295709.3	Q9NRP7-1
	STK36	ENST00000392105.7	TSL:1	c.-89-240G>A		intron	N/A	ENSP00000375954.3	Q9NRP7-2
	STK36	ENST00000925598.1		c.-221G>A		5_prime_UTR	Exon 1 of 27	ENSP00000595657.1

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42476 AN: 151852 Hom.: 7498 Cov.: 31

Gnomad AFR AF: 0.0753

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.0614

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.281

GnomAD4 exome AF: 0.329 AC: 63071 AN: 191924 Hom.: 11403 AF XY: 0.322 AC XY: 33457 AN XY: 103818

African (AFR) AF: 0.0718 AC: 430 AN: 5990

American (AMR) AF: 0.339 AC: 2784 AN: 8206

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 1714 AN: 5092

East Asian (EAS) AF: 0.0597 AC: 555 AN: 9292

South Asian (SAS) AF: 0.271 AC: 8447 AN: 31186

European-Finnish (FIN) AF: 0.381 AC: 3289 AN: 8636

Middle Eastern (MID) AF: 0.247 AC: 193 AN: 780

European-Non Finnish (NFE) AF: 0.376 AC: 42309 AN: 112566

Other (OTH) AF: 0.329 AC: 3350 AN: 10176

GnomAD4 genome AF: 0.280 AC: 42477 AN: 151970 Hom.: 7498 Cov.: 31 AF XY: 0.278 AC XY: 20641 AN XY: 74248

African (AFR) AF: 0.0751 AC: 3117 AN: 41486

American (AMR) AF: 0.336 AC: 5121 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 1216 AN: 3468

East Asian (EAS) AF: 0.0619 AC: 320 AN: 5170

South Asian (SAS) AF: 0.270 AC: 1298 AN: 4810

European-Finnish (FIN) AF: 0.398 AC: 4197 AN: 10548

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.386 AC: 26218 AN: 67920

Other (OTH) AF: 0.283 AC: 597 AN: 2110

Alfa AF: 0.319 Hom.: 1630

Bravo AF: 0.268

Asia WGS AF: 0.178 AC: 621 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.7
DANN	Benign	0.51
PhyloP100		0.18
PromoterAI		0.018	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2241527;

hg19: chr2-219537224;