chr2-218673715-C-G

Variant names:

• chr2-218673715-C-G
• rs1186686334
• NM_015690.5:c.175C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015690.5(STK36):​c.175C>G​(p.Arg59Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: STK36 NM_015690.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.438

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35377517).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK36	NM_015690.5	c.175C>G	p.Arg59Gly	missense_variant	Exon 3 of 27	ENST00000295709.8	NP_056505.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK36	ENST00000295709.8	c.175C>G	p.Arg59Gly	missense_variant	Exon 3 of 27	1	NM_015690.5	ENSP00000295709.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	0.010	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T;.;.;T;.
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.59	D
LIST_S2	Uncertain	0.93	.;D;D;D;D
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.35	T;T;T;T;T
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Benign	0.77	N;N;.;N;.
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-2.7	D;D;D;D;D
REVEL	Benign	0.080
Sift	Benign	0.060	T;T;T;T;T
Sift4G	Benign	0.13	T;T;T;T;T
Polyphen		0.20	B;B;.;B;.
Vest4		0.52
MutPred		0.48		Loss of MoRF binding (P = 0.0454);Loss of MoRF binding (P = 0.0454);.;Loss of MoRF binding (P = 0.0454);Loss of MoRF binding (P = 0.0454);
MVP		0.76
MPC		0.40
ClinPred		0.44	T
GERP RS		2.7
Varity_R		0.30
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs1186686334; hg19: chr2-219538438;