rs2241527

chr2-218672501-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015690.5(STK36):c.-89-240G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 343,894 control chromosomes in the GnomAD database, including 18,901 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.28 (7498 hom., cov: 31)
  • Exomes 𝑓: 0.33 (11403 hom.)
• Consequence: STK36 NM_015690.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.177

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 2-218672501-G-A is Benign according to our data. Variant chr2-218672501-G-A is described in ClinVar as [Benign]. Clinvar id is 1229044.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK36	NM_015690.5	c.-89-240G>A		intron_variant		ENST00000295709.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK36	ENST00000295709.8	c.-89-240G>A		intron_variant		1	NM_015690.5	P1

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42476 AN: 151852 Hom.: 7498 Cov.: 31

Gnomad AFR AF: 0.0753

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.0614

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.281

GnomAD4 exome AF: 0.329 AC: 63071 AN: 191924 Hom.: 11403 AF XY: 0.322 AC XY: 33457 AN XY: 103818

Gnomad4 AFR exome AF: 0.0718

Gnomad4 AMR exome AF: 0.339

Gnomad4 ASJ exome AF: 0.337

Gnomad4 EAS exome AF: 0.0597

Gnomad4 SAS exome AF: 0.271

Gnomad4 FIN exome AF: 0.381

Gnomad4 NFE exome AF: 0.376

Gnomad4 OTH exome AF: 0.329

GnomAD4 genome AF: 0.280 AC: 42477 AN: 151970 Hom.: 7498 Cov.: 31 AF XY: 0.278 AC XY: 20641 AN XY: 74248

Gnomad4 AFR AF: 0.0751

Gnomad4 AMR AF: 0.336

Gnomad4 ASJ AF: 0.351

Gnomad4 EAS AF: 0.0619

Gnomad4 SAS AF: 0.270

Gnomad4 FIN AF: 0.398

Gnomad4 NFE AF: 0.386

Gnomad4 OTH AF: 0.283

Alfa AF: 0.319 Hom.: 1630

Bravo AF: 0.268

Asia WGS AF: 0.178 AC: 621 AN: 3478

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	5.7
Dann	Benign	0.51

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: rs2241527; hg19: chr2-219537224;