rs1344645

Variant names:

• chr2-218673296-G-T
• rs1344645
• NM_015690.5:c.85-329G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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]

STK36 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• ciliary dyskinesia, primary, 46

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
STK36	NM_015690.5	c.85-329G>T		intron_variant	Intron 2 of 26	ENST00000295709.8	NP_056505.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK36	ENST00000295709.8	c.85-329G>T		intron_variant	Intron 2 of 26	1	NM_015690.5	ENSP00000295709.3

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

African (AFR) AF: 0.673 AC: 4962 AN: 7368

American (AMR) AF: 0.405 AC: 3298 AN: 8144

Ashkenazi Jewish (ASJ) AF: 0.392 AC: 3035 AN: 7744

East Asian (EAS) AF: 0.127 AC: 2017 AN: 15848

South Asian (SAS) AF: 0.320 AC: 5866 AN: 18334

European-Finnish (FIN) AF: 0.419 AC: 5367 AN: 12802

Middle Eastern (MID) AF: 0.340 AC: 373 AN: 1096

European-Non Finnish (NFE) AF: 0.417 AC: 61540 AN: 147678

Other (OTH) AF: 0.409 AC: 5854 AN: 14320

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

African (AFR) AF: 0.674 AC: 27927 AN: 41436

American (AMR) AF: 0.427 AC: 6524 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 1390 AN: 3466

East Asian (EAS) AF: 0.138 AC: 716 AN: 5184

South Asian (SAS) AF: 0.324 AC: 1563 AN: 4818

European-Finnish (FIN) AF: 0.428 AC: 4508 AN: 10536

Middle Eastern (MID) AF: 0.353 AC: 103 AN: 292

European-Non Finnish (NFE) AF: 0.425 AC: 28857 AN: 67974

Other (OTH) AF: 0.444 AC: 937 AN: 2110

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
PhyloP100		0.071
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1344645; hg19: chr2-219538019; COSMIC: COSV55309304; COSMIC: COSV55309304;