rs1344645

Positions:

• chr2-218673296-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015690.5(STK36):​c.85-329G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 385,332 control chromosomes in the GnomAD database, including 38,417 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.48 (18832 hom., cov: 32)
  • Exomes 𝑓: 0.40 (19585 hom.)
• Consequence: STK36 NM_015690.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0710

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK36	NM_015690.5	c.85-329G>T		intron_variant		ENST00000295709.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK36	ENST00000295709.8	c.85-329G>T		intron_variant		1	NM_015690.5	P1

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72780 AN: 151880 Hom.: 18791 Cov.: 32

Gnomad AFR AF: 0.674

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.350

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.443

GnomAD4 exome AF: 0.396 AC: 92312 AN: 233334 Hom.: 19585 Cov.: 3 AF XY: 0.390 AC XY: 47156 AN XY: 120964

Gnomad4 AFR exome AF: 0.673

Gnomad4 AMR exome AF: 0.405

Gnomad4 ASJ exome AF: 0.392

Gnomad4 EAS exome AF: 0.127

Gnomad4 SAS exome AF: 0.320

Gnomad4 FIN exome AF: 0.419

Gnomad4 NFE exome AF: 0.417

Gnomad4 OTH exome AF: 0.409

GnomAD4 genome AF: 0.479 AC: 72875 AN: 151998 Hom.: 18832 Cov.: 32 AF XY: 0.472 AC XY: 35043 AN XY: 74288

Gnomad4 AFR AF: 0.674

Gnomad4 AMR AF: 0.427

Gnomad4 ASJ AF: 0.401

Gnomad4 EAS AF: 0.138

Gnomad4 SAS AF: 0.324

Gnomad4 FIN AF: 0.428

Gnomad4 NFE AF: 0.425

Gnomad4 OTH AF: 0.444

Alfa AF: 0.455 Hom.: 3974

Bravo AF: 0.489

Asia WGS AF: 0.274 AC: 955 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.2
DANN	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1344645; hg19: chr2-219538019; COSMIC: COSV55309304; COSMIC: COSV55309304;