2-218675520-CTTTTTTTTTTTTT-CTTTTTTTTTTTTTT

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_015690.5(STK36):​c.434+68dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0605 in 1,130,330 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0054 (1 hom., cov: 27)
  • Exomes 𝑓: 0.067 (3 hom.)
• 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: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, PanelApp Australia
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant 2-218675520-C-CT is Benign according to our data. Variant chr2-218675520-C-CT is described in ClinVar as Benign. ClinVar VariationId is 1272769.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 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.434+68dupT		intron	N/A	NP_056505.2	Q9NRP7-1
	STK36	NM_001369423.1		c.434+68dupT		intron	N/A	NP_001356352.1	Q9NRP7-1
	STK36	NM_001243313.2		c.434+68dupT		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+47_434+48insT		intron	N/A	ENSP00000295709.3	Q9NRP7-1
	STK36	ENST00000392105.7	TSL:1	c.434+47_434+48insT		intron	N/A	ENSP00000375954.3	Q9NRP7-2
	STK36	ENST00000440309.5	TSL:5	c.434+47_434+48insT		intron	N/A	ENSP00000394095.1	Q9NRP7-1

Frequencies

GnomAD3 genomes AF: 0.00542 AC: 622 AN: 114790 Hom.: 1 Cov.: 27

Gnomad AFR AF: 0.00454

Gnomad AMI AF: 0.00668

Gnomad AMR AF: 0.00228

Gnomad ASJ AF: 0.00986

Gnomad EAS AF: 0.00781

Gnomad SAS AF: 0.00363

Gnomad FIN AF: 0.00207

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00664

Gnomad OTH AF: 0.00315

GnomAD2 exomes AF: 0.0516 AC: 3064 AN: 59338 AF XY: 0.0486

Gnomad AFR exome AF: 0.0333

Gnomad AMR exome AF: 0.0663

Gnomad ASJ exome AF: 0.0549

Gnomad EAS exome AF: 0.0690

Gnomad FIN exome AF: 0.0165

Gnomad NFE exome AF: 0.0488

Gnomad OTH exome AF: 0.0591

GnomAD4 exome AF: 0.0668 AC: 67802 AN: 1015538 Hom.: 3 Cov.: 0 AF XY: 0.0664 AC XY: 33413 AN XY: 503256

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

African (AFR) AF: 0.0295 AC: 630 AN: 21374

American (AMR) AF: 0.0585 AC: 1160 AN: 19824

Ashkenazi Jewish (ASJ) AF: 0.0678 AC: 991 AN: 14612

East Asian (EAS) AF: 0.0575 AC: 1421 AN: 24704

South Asian (SAS) AF: 0.0709 AC: 3972 AN: 56060

European-Finnish (FIN) AF: 0.0532 AC: 1269 AN: 23832

Middle Eastern (MID) AF: 0.0603 AC: 162 AN: 2686

European-Non Finnish (NFE) AF: 0.0684 AC: 55579 AN: 812052

Other (OTH) AF: 0.0648 AC: 2618 AN: 40394

⚠️ 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: 0.00542 AC: 622 AN: 114792 Hom.: 1 Cov.: 27 AF XY: 0.00523 AC XY: 286 AN XY: 54722

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

African (AFR) AF: 0.00453 AC: 130 AN: 28688

American (AMR) AF: 0.00228 AC: 26 AN: 11402

Ashkenazi Jewish (ASJ) AF: 0.00986 AC: 29 AN: 2940

East Asian (EAS) AF: 0.00784 AC: 31 AN: 3954

South Asian (SAS) AF: 0.00364 AC: 13 AN: 3568

European-Finnish (FIN) AF: 0.00207 AC: 12 AN: 5794

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 232

European-Non Finnish (NFE) AF: 0.00664 AC: 371 AN: 55870

Other (OTH) AF: 0.00313 AC: 5 AN: 1596

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00631 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

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

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

Other links and lift over

dbSNP: rs33970984;

hg19: chr2-219540243;