2-218675520-CT-C

Position:

• chr2-218675520-CT-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+68del 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

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-CT-C is Benign according to our data. Variant chr2-218675520-CT-C is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK36	NM_015690.5	c.434+68del		intron_variant		ENST00000295709.8	NP_056505.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK36	ENST00000295709.8	c.434+68del		intron_variant		1	NM_015690.5	ENSP00000295709	P1
STK36	ENST00000392105.7	c.434+68del		intron_variant		1		ENSP00000375954
STK36	ENST00000424080.1	c.434+68del		intron_variant		5		ENSP00000403527
STK36	ENST00000440309.5	c.434+68del		intron_variant		5		ENSP00000394095	P1

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

GnomAD3 exomes AF: 0.202 AC: 11990 AN: 59338 Hom.: 3 AF XY: 0.193 AC XY: 6032 AN XY: 31242

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 SAS exome AF: 0.205

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

Gnomad4 AFR exome AF: 0.325

Gnomad4 AMR exome AF: 0.236

Gnomad4 ASJ exome AF: 0.237

Gnomad4 EAS exome AF: 0.229

Gnomad4 SAS exome AF: 0.231

Gnomad4 FIN exome AF: 0.206

Gnomad4 NFE exome AF: 0.252

Gnomad4 OTH exome AF: 0.252

GnomAD4 genome AF: 0.0910 AC: 10449 AN: 114796 Hom.: 1176 Cov.: 27 AF XY: 0.0884 AC XY: 4839 AN XY: 54732

Gnomad4 AFR AF: 0.323

Gnomad4 AMR AF: 0.0483

Gnomad4 ASJ AF: 0.0163

Gnomad4 EAS AF: 0.00303

Gnomad4 SAS AF: 0.0112

Gnomad4 FIN AF: 0.00483

Gnomad4 NFE AF: 0.00637

Gnomad4 OTH AF: 0.0901

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 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs33970984; hg19: chr2-219540243;