2-218675520-CTTTTTTTTTTT-CTTTTTTTTTTTTTT

Variant names:

• chr2-218675520-C-CTTT
• rs33970984
• NM_015690.5:c.434+66_434+68dupTTT

Variant summary

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

The NM_015690.5(STK36):​c.434+66_434+68dupTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000384 in 1,147,198 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000070 (0 hom., cov: 27)
  • Exomes 𝑓: 0.00042 (0 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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK36	NM_015690.5	c.434+66_434+68dupTTT		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+48insTTT		intron_variant	Intron 5 of 26	1	NM_015690.5	ENSP00000295709.3

Frequencies

GnomAD3 genomes AF: 0.0000697 AC: 8 AN: 114852 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.0000349

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000878

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000252

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000894

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000419 AC: 433 AN: 1032346 Hom.: 0 Cov.: 0 AF XY: 0.000434 AC XY: 222 AN XY: 511740

Gnomad4 AFR exome AF: 0.000185

Gnomad4 AMR exome AF: 0.000445

Gnomad4 ASJ exome AF: 0.000539

Gnomad4 EAS exome AF: 0.000558

Gnomad4 SAS exome AF: 0.000942

Gnomad4 FIN exome AF: 0.000870

Gnomad4 NFE exome AF: 0.000372

Gnomad4 OTH exome AF: 0.000367

GnomAD4 genome AF: 0.0000697 AC: 8 AN: 114852 Hom.: 0 Cov.: 27 AF XY: 0.0000365 AC XY: 2 AN XY: 54720

Gnomad4 AFR AF: 0.0000349

Gnomad4 AMR AF: 0.0000878

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000252

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000894

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;