Genetic Variant STK36:c.303+120A>T (chr2-218674076-A-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.34

Publications

0 publications found

Variant links:

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)

STK36 links:

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ACMG classification

Classification was made for transcript

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).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015690.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
STK36	NM_015690.5	MANE Select	c.303+120A>T	intron	N/A	NP_056505.2
STK36	NM_001369423.1		c.303+120A>T	intron	N/A	NP_001356352.1
STK36	NM_001243313.2		c.303+120A>T	intron	N/A	NP_001230242.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
STK36	ENST00000295709.8	TSL:1 MANE Select	c.303+120A>T	intron	N/A	ENSP00000295709.3
STK36	ENST00000392105.7	TSL:1	c.303+120A>T	intron	N/A	ENSP00000375954.3
STK36	ENST00000440309.5	TSL:5	c.303+120A>T	intron	N/A	ENSP00000394095.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000252

AC:

AN:

792740

Hom.:

AF XY:

0.00

AC XY:

AN XY:

406686

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

19066

American (AMR)

AF:

0.00

AC:

AN:

24184

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17326

East Asian (EAS)

AF:

0.00

AC:

AN:

33054

South Asian (SAS)

AF:

0.00

AC:

AN:

55732

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39946

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2786

European-Non Finnish (NFE)

AF:

0.00000355

AC:

AN:

562704

Other (OTH)

AF:

0.00

AC:

AN:

37942

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over