2-218675520-CTTTTTTTTTTTTT-CTTTTTTTTTTTT

Variant names:

• chr2-218675520-CT-C
• rs33970984
• NM_015690.5:c.434+68delT

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+68delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.091 in 114,796 control chromosomes in the GnomAD database, including 1,176 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.091 (1176 hom., cov: 27)
  • Exomes 𝑓: 0.25 (51 hom.)
  • Failed GnomAD Quality Control
• Consequence: STK36 NM_015690.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0100
• 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 2-218675520-CT-C is Benign according to our data. Variant chr2-218675520-CT-C is described in ClinVar as Benign. ClinVar VariationId is 1178774.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.318 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+68delT		intron	N/A	NP_056505.2	Q9NRP7-1
	STK36	NM_001369423.1		c.434+68delT		intron	N/A	NP_001356352.1	Q9NRP7-1
	STK36	NM_001243313.2		c.434+68delT		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+48delT		intron	N/A	ENSP00000295709.3	Q9NRP7-1
	STK36	ENST00000392105.7	TSL:1	c.434+48delT		intron	N/A	ENSP00000375954.3	Q9NRP7-2
	STK36	ENST00000440309.5	TSL:5	c.434+48delT		intron	N/A	ENSP00000394095.1	Q9NRP7-1

Frequencies

GnomAD3 genomes AF: 0.0909 AC: 10439 AN: 114794 Hom.: 1175 Cov.: 27

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0484

Gnomad ASJ AF: 0.0163

Gnomad EAS AF: 0.00302

Gnomad SAS AF: 0.0112

Gnomad FIN AF: 0.00483

Gnomad MID AF: 0.0748

Gnomad NFE AF: 0.00637

Gnomad OTH AF: 0.0912

GnomAD2 exomes AF: 0.202 AC: 11990 AN: 59338 AF XY: 0.193

Gnomad AFR exome AF: 0.247

Gnomad AMR exome AF: 0.277

Gnomad ASJ exome AF: 0.225

Gnomad EAS exome AF: 0.223

Gnomad FIN exome AF: 0.115

Gnomad NFE exome AF: 0.167

Gnomad OTH exome AF: 0.244

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.250 AC: 247510 AN: 989400 Hom.: 51 Cov.: 0 AF XY: 0.248 AC XY: 121812 AN XY: 490236

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

African (AFR) AF: 0.325 AC: 6886 AN: 21164

American (AMR) AF: 0.236 AC: 4604 AN: 19522

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 3414 AN: 14432

East Asian (EAS) AF: 0.229 AC: 5575 AN: 24354

South Asian (SAS) AF: 0.231 AC: 12692 AN: 54980

European-Finnish (FIN) AF: 0.206 AC: 4812 AN: 23394

Middle Eastern (MID) AF: 0.249 AC: 653 AN: 2622

European-Non Finnish (NFE) AF: 0.252 AC: 198931 AN: 789512

Other (OTH) AF: 0.252 AC: 9943 AN: 39420

⚠️ 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: 0.0910 AC: 10449 AN: 114796 Hom.: 1176 Cov.: 27 AF XY: 0.0884 AC XY: 4839 AN XY: 54732

African (AFR) AF: 0.323 AC: 9252 AN: 28632

American (AMR) AF: 0.0483 AC: 551 AN: 11408

Ashkenazi Jewish (ASJ) AF: 0.0163 AC: 48 AN: 2944

East Asian (EAS) AF: 0.00303 AC: 12 AN: 3954

South Asian (SAS) AF: 0.0112 AC: 40 AN: 3572

European-Finnish (FIN) AF: 0.00483 AC: 28 AN: 5796

Middle Eastern (MID) AF: 0.0776 AC: 18 AN: 232

European-Non Finnish (NFE) AF: 0.00637 AC: 356 AN: 55912

Other (OTH) AF: 0.0901 AC: 144 AN: 1598

Alfa AF: 0.00891 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		0.010
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

Other links and lift over

dbSNP: rs33970984; hg19: chr2-219540243; COSMIC: COSV107340864; COSMIC: COSV107340864;