chr2-218675520-CTTTTTTTTTTTT-C

Variant names:

• chr2-218675520-CTTTTTTTTTTTT-C
• rs33970984
• NM_015690.5:c.434+57_434+68delTTTTTTTTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_015690.5(STK36):​c.434+57_434+68delTTTTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000484 in 1,033,440 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 27)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: STK36 NM_015690.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

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+57_434+68delTTTTTTTTTTTT		intron	N/A	NP_056505.2	Q9NRP7-1
	STK36	NM_001369423.1		c.434+57_434+68delTTTTTTTTTTTT		intron	N/A	NP_001356352.1	Q9NRP7-1
	STK36	NM_001243313.2		c.434+57_434+68delTTTTTTTTTTTT		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+59delTTTTTTTTTTTT		intron	N/A	ENSP00000295709.3	Q9NRP7-1
	STK36	ENST00000392105.7	TSL:1	c.434+48_434+59delTTTTTTTTTTTT		intron	N/A	ENSP00000375954.3	Q9NRP7-2
	STK36	ENST00000440309.5	TSL:5	c.434+48_434+59delTTTTTTTTTTTT		intron	N/A	ENSP00000394095.1	Q9NRP7-1

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome AF: 0.00000484 AC: 5 AN: 1033440 Hom.: 0 AF XY: 0.00000781 AC XY: 4 AN XY: 512334

African (AFR) AF: 0.0000463 AC: 1 AN: 21618

American (AMR) AF: 0.00 AC: 0 AN: 20256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14854

East Asian (EAS) AF: 0.00 AC: 0 AN: 25138

South Asian (SAS) AF: 0.0000174 AC: 1 AN: 57458

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24144

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2704

European-Non Finnish (NFE) AF: 0.00000242 AC: 2 AN: 826294

Other (OTH) AF: 0.0000244 AC: 1 AN: 40974

GnomAD4 genome Cov.: 27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs33970984; hg19: chr2-219540243;