2-218675267-A-G

Position:

• chr2-218675267-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015690.5(STK36):​c.304-76A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0115 in 1,519,200 control chromosomes in the GnomAD database, including 1,659 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.060 (917 hom., cov: 32)
  • Exomes 𝑓: 0.0060 (742 hom.)
• Consequence: STK36 NM_015690.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0480

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 2-218675267-A-G is Benign according to our data. Variant chr2-218675267-A-G is described in ClinVar as [Benign]. Clinvar id is 1266281.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK36	NM_015690.5	c.304-76A>G		intron_variant		ENST00000295709.8	NP_056505.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK36	ENST00000295709.8	c.304-76A>G		intron_variant		1	NM_015690.5	ENSP00000295709	P1

Frequencies

GnomAD3 genomes AF: 0.0601 AC: 9141 AN: 152192 Hom.: 915 Cov.: 32

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0225

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000808

Gnomad OTH AF: 0.0473

GnomAD4 exome AF: 0.00604 AC: 8255 AN: 1366890 Hom.: 742 AF XY: 0.00521 AC XY: 3536 AN XY: 678442

Gnomad4 AFR exome AF: 0.214

Gnomad4 AMR exome AF: 0.0117

Gnomad4 ASJ exome AF: 0.0000860

Gnomad4 EAS exome AF: 0.0000258

Gnomad4 SAS exome AF: 0.000724

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000359

Gnomad4 OTH exome AF: 0.0140

GnomAD4 genome AF: 0.0601 AC: 9153 AN: 152310 Hom.: 917 Cov.: 32 AF XY: 0.0592 AC XY: 4409 AN XY: 74494

Gnomad4 AFR AF: 0.208

Gnomad4 AMR AF: 0.0224

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000808

Gnomad4 OTH AF: 0.0463

Alfa AF: 0.0475 Hom.: 59

Bravo AF: 0.0685

Asia WGS AF: 0.0120 AC: 41 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 15, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.30
DANN	Benign	0.58

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: rs73079025; hg19: chr2-219539990;