2-218674076-A-T

Variant names:

• chr2-218674076-A-T
• rs7604319
• NM_015690.5:c.303+120A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015690.5(STK36):​c.303+120A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000252 in 792,740 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000025 (0 hom.)
• Consequence: STK36 NM_015690.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.34
• Publications: 0 publications found

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]

STK36 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• ciliary dyskinesia, primary, 46

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK36	NM_015690.5	c.303+120A>T		intron_variant	Intron 4 of 26	ENST00000295709.8	NP_056505.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK36	ENST00000295709.8	c.303+120A>T		intron_variant	Intron 4 of 26	1	NM_015690.5	ENSP00000295709.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000252 AC: 2 AN: 792740 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 406686

African (AFR) AF: 0.00 AC: 0 AN: 19066

American (AMR) AF: 0.00 AC: 0 AN: 24184

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17326

East Asian (EAS) AF: 0.00 AC: 0 AN: 33054

South Asian (SAS) AF: 0.00 AC: 0 AN: 55732

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39946

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2786

European-Non Finnish (NFE) AF: 0.00000355 AC: 2 AN: 562704

Other (OTH) AF: 0.00 AC: 0 AN: 37942

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	11
DANN	Benign	0.77
PhyloP100		1.3

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

Other links and lift over

dbSNP: rs7604319; hg19: chr2-219538799; COSMIC: COSV55308153; COSMIC: COSV55308153;