2-218675543-A-T

Variant names:

• chr2-218675543-A-T
• rs143680180
• NM_015690.5:c.434+70A>T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_015690.5(STK36):​c.434+70A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.0019 (0 hom., cov: 21)
  • Exomes 𝑓: 0.000027 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: STK36 NM_015690.5 intron
• Clinical Significance: Not reported in ClinVar
• 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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK36	NM_015690.5	c.434+70A>T		intron_variant	Intron 5 of 26	ENST00000295709.8	NP_056505.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK36	ENST00000295709.8	c.434+70A>T		intron_variant	Intron 5 of 26	1	NM_015690.5	ENSP00000295709.3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 168 AN: 90110 Hom.: 0 Cov.: 21 FAILED QC

Gnomad AFR AF: 0.000572

Gnomad AMI AF: 0.00370

Gnomad AMR AF: 0.00234

Gnomad ASJ AF: 0.00256

Gnomad EAS AF: 0.000737

Gnomad SAS AF: 0.000761

Gnomad FIN AF: 0.00226

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00259

Gnomad OTH AF: 0.00253

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000270 AC: 27 AN: 1001692 Hom.: 0 AF XY: 0.0000118 AC XY: 6 AN XY: 506876

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000316

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000640

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000281

Gnomad4 OTH exome AF: 0.0000714

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00186 AC: 168 AN: 90150 Hom.: 0 Cov.: 21 AF XY: 0.00146 AC XY: 61 AN XY: 41736

Gnomad4 AFR AF: 0.000571

Gnomad4 AMR AF: 0.00234

Gnomad4 ASJ AF: 0.00256

Gnomad4 EAS AF: 0.000737

Gnomad4 SAS AF: 0.000763

Gnomad4 FIN AF: 0.00226

Gnomad4 NFE AF: 0.00259

Gnomad4 OTH AF: 0.00251

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	5.6
DANN	Benign	0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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;