chr2-168173254-A-G

Variant names:

• chr2-168173254-A-G
• rs2390639
• NM_013233.3:c.322-5847T>C

Variant summary

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

The NM_013233.3(STK39):​c.322-5847T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 152,036 control chromosomes in the GnomAD database, including 5,711 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 0.26 (5711 hom., cov: 32)
• Consequence: STK39 NM_013233.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.205
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK39	NM_013233.3	c.322-5847T>C		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.322-5847T>C		intron_variant	Intron 2 of 17	1	NM_013233.3	ENSP00000348278.4
STK39	ENST00000697205.1	c.322-5847T>C		intron_variant	Intron 2 of 16			ENSP00000513185.1

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39315 AN: 151918 Hom.: 5700 Cov.: 32

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.560

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.259 AC: 39372 AN: 152036 Hom.: 5711 Cov.: 32 AF XY: 0.262 AC XY: 19475 AN XY: 74330

African (AFR) AF: 0.336 AC: 13939 AN: 41462

American (AMR) AF: 0.283 AC: 4317 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 844 AN: 3470

East Asian (EAS) AF: 0.561 AC: 2903 AN: 5178

South Asian (SAS) AF: 0.296 AC: 1426 AN: 4812

European-Finnish (FIN) AF: 0.248 AC: 2619 AN: 10576

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12584 AN: 67956

Other (OTH) AF: 0.260 AC: 548 AN: 2110

Alfa AF: 0.219 Hom.: 1725

Bravo AF: 0.267

Asia WGS AF: 0.402 AC: 1399 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.2
DANN	Benign	0.49
PhyloP100		0.20
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: rs2390639; hg19: chr2-169029764;