2-218675520-CTTTTTTTTTTT-CTTTTTTTTTTTTT

Variant names:

• chr2-218675520-C-CTT
• rs33970984
• NM_015690.5:c.434+67_434+68dupTT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_015690.5(STK36):​c.434+67_434+68dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00423 in 1,141,238 control chromosomes in the GnomAD database, including 2 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00089 (0 hom., cov: 27)
  • Exomes 𝑓: 0.0046 (2 hom.)
• Consequence: STK36 NM_015690.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0100

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.

• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK36	NM_015690.5	c.434+67_434+68dupTT		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+47_434+48insTT		intron_variant	Intron 5 of 26	1	NM_015690.5	ENSP00000295709.3

Frequencies

GnomAD3 genomes AF: 0.000889 AC: 102 AN: 114774 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.000349

Gnomad AMI AF: 0.00402

Gnomad AMR AF: 0.000439

Gnomad ASJ AF: 0.000341

Gnomad EAS AF: 0.00101

Gnomad SAS AF: 0.00112

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00134

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00664 AC: 394 AN: 59338 Hom.: 0 AF XY: 0.00608 AC XY: 190 AN XY: 31242

Gnomad AFR exome AF: 0.00406

Gnomad AMR exome AF: 0.00744

Gnomad ASJ exome AF: 0.00619

Gnomad EAS exome AF: 0.0104

Gnomad SAS exome AF: 0.00456

Gnomad FIN exome AF: 0.00143

Gnomad NFE exome AF: 0.00691

Gnomad OTH exome AF: 0.00917

GnomAD4 exome AF: 0.00461 AC: 4731 AN: 1026462 Hom.: 2 Cov.: 0 AF XY: 0.00465 AC XY: 2367 AN XY: 508790

Gnomad4 AFR exome AF: 0.00232

Gnomad4 AMR exome AF: 0.00453

Gnomad4 ASJ exome AF: 0.00542

Gnomad4 EAS exome AF: 0.00457

Gnomad4 SAS exome AF: 0.00760

Gnomad4 FIN exome AF: 0.00621

Gnomad4 NFE exome AF: 0.00435

Gnomad4 OTH exome AF: 0.00590

GnomAD4 genome AF: 0.000889 AC: 102 AN: 114776 Hom.: 0 Cov.: 27 AF XY: 0.000932 AC XY: 51 AN XY: 54720

Gnomad4 AFR AF: 0.000349

Gnomad4 AMR AF: 0.000438

Gnomad4 ASJ AF: 0.000341

Gnomad4 EAS AF: 0.00101

Gnomad4 SAS AF: 0.00112

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00134

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs33970984; hg19: chr2-219540243;