2-218675520-CTTT-C

Variant names:

• chr2-218675519-TCTT-TC
• rs33970984
• NM_015690.5:c.434+67_434+68delTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_015690.5(STK36):​c.434+67_434+68delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0871 in 1,095,578 control chromosomes in the GnomAD database, including 77 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.035 (55 hom., cov: 27)
  • Exomes 𝑓: 0.093 (22 hom.)
• Consequence: STK36 NM_015690.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.12
• 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 -10 ACMG points.

• BP6: Variant 2-218675519-TCTT-TC is Benign according to our data. Variant chr2-218675520-CTT-C is described in ClinVar as Benign. ClinVar VariationId is 1280757.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.074 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.434+67_434+68delTT		intron	N/A	NP_056505.2	Q9NRP7-1
	STK36	NM_001369423.1		c.434+67_434+68delTT		intron	N/A	NP_001356352.1	Q9NRP7-1
	STK36	NM_001243313.2		c.434+67_434+68delTT		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.434+48_434+49delTT		intron	N/A	ENSP00000295709.3	Q9NRP7-1
	STK36	ENST00000392105.7	TSL:1	c.434+48_434+49delTT		intron	N/A	ENSP00000375954.3	Q9NRP7-2
	STK36	ENST00000440309.5	TSL:5	c.434+48_434+49delTT		intron	N/A	ENSP00000394095.1	Q9NRP7-1

Frequencies

GnomAD3 genomes AF: 0.0352 AC: 4037 AN: 114706 Hom.: 55 Cov.: 27

Gnomad AFR AF: 0.0353

Gnomad AMI AF: 0.0254

Gnomad AMR AF: 0.0206

Gnomad ASJ AF: 0.0354

Gnomad EAS AF: 0.0813

Gnomad SAS AF: 0.0436

Gnomad FIN AF: 0.0204

Gnomad MID AF: 0.0238

Gnomad NFE AF: 0.0360

Gnomad OTH AF: 0.0360

GnomAD2 exomes AF: 0.107 AC: 6325 AN: 59338 AF XY: 0.105

Gnomad AFR exome AF: 0.155

Gnomad AMR exome AF: 0.116

Gnomad ASJ exome AF: 0.0888

Gnomad EAS exome AF: 0.143

Gnomad FIN exome AF: 0.0819

Gnomad NFE exome AF: 0.0903

Gnomad OTH exome AF: 0.0969

GnomAD4 exome AF: 0.0932 AC: 91411 AN: 980870 Hom.: 22 AF XY: 0.0933 AC XY: 45254 AN XY: 485236

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.146 AC: 3034 AN: 20752

American (AMR) AF: 0.0962 AC: 1787 AN: 18568

Ashkenazi Jewish (ASJ) AF: 0.0978 AC: 1384 AN: 14148

East Asian (EAS) AF: 0.122 AC: 2904 AN: 23712

South Asian (SAS) AF: 0.0980 AC: 5222 AN: 53260

European-Finnish (FIN) AF: 0.0964 AC: 2218 AN: 23002

Middle Eastern (MID) AF: 0.105 AC: 268 AN: 2544

European-Non Finnish (NFE) AF: 0.0901 AC: 70792 AN: 785948

Other (OTH) AF: 0.0976 AC: 3802 AN: 38936

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0352 AC: 4037 AN: 114708 Hom.: 55 Cov.: 27 AF XY: 0.0338 AC XY: 1846 AN XY: 54690

African (AFR) AF: 0.0352 AC: 1011 AN: 28690

American (AMR) AF: 0.0208 AC: 237 AN: 11406

Ashkenazi Jewish (ASJ) AF: 0.0354 AC: 104 AN: 2942

East Asian (EAS) AF: 0.0813 AC: 320 AN: 3934

South Asian (SAS) AF: 0.0435 AC: 155 AN: 3566

European-Finnish (FIN) AF: 0.0204 AC: 118 AN: 5784

Middle Eastern (MID) AF: 0.0261 AC: 6 AN: 230

European-Non Finnish (NFE) AF: 0.0360 AC: 2010 AN: 55816

Other (OTH) AF: 0.0358 AC: 57 AN: 1592

Alfa AF: 0.00914 Hom.: 2

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs33970984; hg19: chr2-219540242;