chr2-218676057-A-T

Position:

• chr2-218676057-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015690.5(STK36):​c.463A>T​(p.Met155Leu) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: STK36 NM_015690.5 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 1.69

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13741565).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK36	NM_015690.5	c.463A>T	p.Met155Leu	missense_variant	6/27	ENST00000295709.8	NP_056505.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK36	ENST00000295709.8	c.463A>T	p.Met155Leu	missense_variant	6/27	1	NM_015690.5	ENSP00000295709	P1
STK36	ENST00000392105.7	c.463A>T	p.Met155Leu	missense_variant	6/27	1		ENSP00000375954
STK36	ENST00000440309.5	c.463A>T	p.Met155Leu	missense_variant	6/27	5		ENSP00000394095	P1
STK36	ENST00000424080.1	c.463A>T	p.Met155Leu	missense_variant	6/8	5		ENSP00000403527

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

STK36-related disorder Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 27, 2024

The STK36 c.463A>T variant is predicted to result in the amino acid substitution p.Met155Leu. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	21
DANN	Benign	0.92
DEOGEN2	Benign	0.076	T;.;T;.
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.91	.;D;D;D
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.14	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.44	N;N;N;.
MutationTaster	Benign	0.97	D;D;D;D
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.65	N;N;N;N
REVEL	Benign	0.086
Sift	Benign	0.61	T;T;T;T
Sift4G	Benign	0.76	T;T;T;T
Polyphen		0.0090	B;B;B;.
Vest4		0.26
MutPred		0.50		Gain of catalytic residue at M155 (P = 0.1327);Gain of catalytic residue at M155 (P = 0.1327);Gain of catalytic residue at M155 (P = 0.1327);Gain of catalytic residue at M155 (P = 0.1327);
MVP		0.72
MPC		0.16
ClinPred		0.77	D
GERP RS		5.7
Varity_R		0.15
gMVP		0.28

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-219540780;