2-218675520-CTTTTTTTTTTT-CTTTTTTTT

Variant names:

• chr2-218675520-CTTT-C
• rs33970984
• NM_015690.5:c.434+66_434+68delTTT

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The NM_015690.5(STK36):​c.434+66_434+68delTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0179 in 1,120,178 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000035 (0 hom., cov: 27)
  • Exomes 𝑓: 0.020 (0 hom.)
• Consequence: STK36 NM_015690.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.02 (20057/1005316) while in subpopulation AFR AF= 0.0343 (720/21010). AF 95% confidence interval is 0.0322. There are 0 homozygotes in gnomad4_exome. There are 9971 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK36	NM_015690.5	c.434+66_434+68delTTT		intron_variant	Intron 5 of 26	ENST00000295709.8	NP_056505.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK36	ENST00000295709.8	c.434+48_434+50delTTT		intron_variant	Intron 5 of 26	1	NM_015690.5	ENSP00000295709.3
STK36	ENST00000392105.7	c.434+48_434+50delTTT		intron_variant	Intron 5 of 26	1		ENSP00000375954.3
STK36	ENST00000440309.5	c.434+48_434+50delTTT		intron_variant	Intron 5 of 26	5		ENSP00000394095.1
STK36	ENST00000424080.1	c.434+48_434+50delTTT		intron_variant	Intron 5 of 7	5		ENSP00000403527.1

Frequencies

GnomAD3 genomes AF: 0.0000348 AC: 4 AN: 114860 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000878

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000173

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000358

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0352 AC: 2086 AN: 59338 Hom.: 1 AF XY: 0.0358 AC XY: 1118 AN XY: 31242

Gnomad AFR exome AF: 0.0448

Gnomad AMR exome AF: 0.0303

Gnomad ASJ exome AF: 0.0268

Gnomad EAS exome AF: 0.0424

Gnomad SAS exome AF: 0.0372

Gnomad FIN exome AF: 0.0408

Gnomad NFE exome AF: 0.0336

Gnomad OTH exome AF: 0.0298

GnomAD4 exome AF: 0.0200 AC: 20057 AN: 1005316 Hom.: 0 AF XY: 0.0200 AC XY: 9971 AN XY: 498026

Gnomad4 AFR exome AF: 0.0343

Gnomad4 AMR exome AF: 0.0210

Gnomad4 ASJ exome AF: 0.0268

Gnomad4 EAS exome AF: 0.0339

Gnomad4 SAS exome AF: 0.0209

Gnomad4 FIN exome AF: 0.0262

Gnomad4 NFE exome AF: 0.0186

Gnomad4 OTH exome AF: 0.0227

GnomAD4 genome AF: 0.0000348 AC: 4 AN: 114862 Hom.: 0 Cov.: 27 AF XY: 0.0000548 AC XY: 3 AN XY: 54748

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000877

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000173

Gnomad4 NFE AF: 0.0000358

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs33970984; hg19: chr2-219540243;