2-218675520-CTT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_015690.5(STK36):c.434+67_434+68del 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

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 Benign. Variant got -10 ACMG points.

• BP6: Variant 2-218675520-CTT-C is Benign according to our data. Variant chr2-218675520-CTT-C is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK36	NM_015690.5	c.434+67_434+68del		intron_variant		ENST00000295709.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK36	ENST00000295709.8	c.434+67_434+68del		intron_variant		1	NM_015690.5	P1
STK36	ENST00000392105.7	c.434+67_434+68del		intron_variant		1
STK36	ENST00000424080.1	c.434+67_434+68del		intron_variant		5
STK36	ENST00000440309.5	c.434+67_434+68del		intron_variant		5		P1

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

GnomAD3 exomes AF: 0.107 AC: 6325 AN: 59338 Hom.: 1 AF XY: 0.105 AC XY: 3283 AN XY: 31242

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 SAS exome AF: 0.112

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

Gnomad4 AFR exome AF: 0.146

Gnomad4 AMR exome AF: 0.0962

Gnomad4 ASJ exome AF: 0.0978

Gnomad4 EAS exome AF: 0.122

Gnomad4 SAS exome AF: 0.0980

Gnomad4 FIN exome AF: 0.0964

Gnomad4 NFE exome AF: 0.0901

Gnomad4 OTH exome AF: 0.0976

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

Gnomad4 AFR AF: 0.0352

Gnomad4 AMR AF: 0.0208

Gnomad4 ASJ AF: 0.0354

Gnomad4 EAS AF: 0.0813

Gnomad4 SAS AF: 0.0435

Gnomad4 FIN AF: 0.0204

Gnomad4 NFE AF: 0.0360

Gnomad4 OTH AF: 0.0358

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 20, 2021

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Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs33970984; hg19: chr2-219540243;