2-168178225-C-T

Variant names:

• chr2-168178225-C-T
• rs2203703
• NM_013233.3:c.321+3753G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013233.3(STK39):​c.321+3753G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 152,070 control chromosomes in the GnomAD database, including 6,934 homozygotes. 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: 𝑓 0.28 (6934 hom., cov: 32)
• Consequence: STK39 NM_013233.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0600
• Publications: 4 publications found

Genes affected

STK39 (HGNC:17717): (serine/threonine kinase 39) This gene encodes a serine/threonine kinase that is thought to function in the cellular stress response pathway. The kinase is activated in response to hypotonic stress, leading to phosphorylation of several cation-chloride-coupled cotransporters. The catalytically active kinase specifically activates the p38 MAP kinase pathway, and its interaction with p38 decreases upon cellular stress, suggesting that this kinase may serve as an intermediate in the response to cellular stress. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK39	NM_013233.3	c.321+3753G>A		intron_variant	Intron 2 of 17	ENST00000355999.5	NP_037365.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK39	ENST00000355999.5	c.321+3753G>A		intron_variant	Intron 2 of 17	1	NM_013233.3	ENSP00000348278.4
STK39	ENST00000697205.1	c.321+3753G>A		intron_variant	Intron 2 of 16			ENSP00000513185.1

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42583 AN: 151952 Hom.: 6919 Cov.: 32

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.561

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.270

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.280 AC: 42649 AN: 152070 Hom.: 6934 Cov.: 32 AF XY: 0.283 AC XY: 21016 AN XY: 74324

African (AFR) AF: 0.412 AC: 17082 AN: 41480

American (AMR) AF: 0.292 AC: 4455 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 844 AN: 3468

East Asian (EAS) AF: 0.562 AC: 2901 AN: 5166

South Asian (SAS) AF: 0.296 AC: 1423 AN: 4804

European-Finnish (FIN) AF: 0.247 AC: 2609 AN: 10548

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12563 AN: 68008

Other (OTH) AF: 0.274 AC: 579 AN: 2112

Alfa AF: 0.240 Hom.: 858

Bravo AF: 0.292

Asia WGS AF: 0.407 AC: 1415 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.0
DANN	Benign	0.76
PhyloP100		-0.060
Mutation Taster		=100/0	polymorphism (auto)

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: rs2203703; hg19: chr2-169034735;