rs7604319

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr2-218674076-A-C
• chr2-218674076-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015690.5(STK36):​c.303+120A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 943,152 control chromosomes in the GnomAD database, including 59,047 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (7492 hom., cov: 32)
  • Exomes 𝑓: 0.35 (51555 hom.)
• Consequence: STK36 NM_015690.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.34
• Publications: 11 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 2-218674076-A-C is Benign according to our data. Variant chr2-218674076-A-C is described in ClinVar as Benign. ClinVar VariationId is 1268211.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42293 AN: 152028 Hom.: 7492 Cov.: 32

Gnomad AFR AF: 0.0699

Gnomad AMI AF: 0.358

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.0614

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.282

GnomAD4 exome AF: 0.348 AC: 275324 AN: 791006 Hom.: 51555 AF XY: 0.346 AC XY: 140435 AN XY: 405884

African (AFR) AF: 0.0634 AC: 1208 AN: 19064

American (AMR) AF: 0.343 AC: 8279 AN: 24150

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 5975 AN: 17302

East Asian (EAS) AF: 0.0617 AC: 2039 AN: 33054

South Asian (SAS) AF: 0.277 AC: 15447 AN: 55674

European-Finnish (FIN) AF: 0.394 AC: 15715 AN: 39872

Middle Eastern (MID) AF: 0.259 AC: 720 AN: 2780

European-Non Finnish (NFE) AF: 0.381 AC: 213556 AN: 561240

Other (OTH) AF: 0.327 AC: 12385 AN: 37870

GnomAD4 genome AF: 0.278 AC: 42292 AN: 152146 Hom.: 7492 Cov.: 32 AF XY: 0.277 AC XY: 20567 AN XY: 74354

African (AFR) AF: 0.0697 AC: 2894 AN: 41548

American (AMR) AF: 0.335 AC: 5111 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 1219 AN: 3470

East Asian (EAS) AF: 0.0619 AC: 321 AN: 5186

South Asian (SAS) AF: 0.271 AC: 1305 AN: 4820

European-Finnish (FIN) AF: 0.399 AC: 4209 AN: 10558

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.386 AC: 26244 AN: 67986

Other (OTH) AF: 0.283 AC: 598 AN: 2110

Alfa AF: 0.326 Hom.: 1123

Bravo AF: 0.266

Asia WGS AF: 0.178 AC: 620 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 15, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	11
DANN	Benign	0.69
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;