chr2-218675543-A-G

Position:

• chr2-218675543-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.434+70A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0141 in 1,091,832 control chromosomes in the GnomAD database, including 1,480 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.090 (802 hom., cov: 21)
  • Exomes 𝑓: 0.0073 (678 hom.)
• Consequence: STK36 NM_015690.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.40

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=-0.95).
• BP6: Variant 2-218675543-A-G is Benign according to our data. Variant chr2-218675543-A-G is described in ClinVar as [Benign]. Clinvar id is 1231128.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK36	NM_015690.5	c.434+70A>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.434+70A>G		intron_variant		1	NM_015690.5	ENSP00000295709	P1
STK36	ENST00000392105.7	c.434+70A>G		intron_variant		1		ENSP00000375954
STK36	ENST00000424080.1	c.434+70A>G		intron_variant		5		ENSP00000403527
STK36	ENST00000440309.5	c.434+70A>G		intron_variant		5		ENSP00000394095	P1

Frequencies

GnomAD3 genomes AF: 0.0901 AC: 8112 AN: 90016 Hom.: 802 Cov.: 21

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0464

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00114

Gnomad FIN AF: 0.000752

Gnomad MID AF: 0.0439

Gnomad NFE AF: 0.00127

Gnomad OTH AF: 0.0724

GnomAD4 exome AF: 0.00731 AC: 7320 AN: 1001776 Hom.: 678 AF XY: 0.00628 AC XY: 3184 AN XY: 506908

Gnomad4 AFR exome AF: 0.233

Gnomad4 AMR exome AF: 0.0108

Gnomad4 ASJ exome AF: 0.0000543

Gnomad4 EAS exome AF: 0.0000320

Gnomad4 SAS exome AF: 0.000833

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000464

Gnomad4 OTH exome AF: 0.0163

GnomAD4 genome AF: 0.0901 AC: 8115 AN: 90056 Hom.: 802 Cov.: 21 AF XY: 0.0937 AC XY: 3905 AN XY: 41692

Gnomad4 AFR AF: 0.291

Gnomad4 AMR AF: 0.0462

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00114

Gnomad4 FIN AF: 0.000752

Gnomad4 NFE AF: 0.00127

Gnomad4 OTH AF: 0.0711

Alfa AF: 0.000372 Hom.: 0

Bravo AF: 0.0681

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	-0.95
CADD	Benign	1.9
DANN	Benign	0.34

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: rs143680180; hg19: chr2-219540266;