2-168173254-A-G

Position:

• chr2-168173254-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
STK39	NM_013233.3	c.322-5847T>C		intron_variant		ENST00000355999.5	NP_037365.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK39	ENST00000355999.5	c.322-5847T>C		intron_variant		1	NM_013233.3	ENSP00000348278	P1
STK39	ENST00000697205.1	c.322-5847T>C		intron_variant				ENSP00000513185

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

Gnomad4 AFR AF: 0.336

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.243

Gnomad4 EAS AF: 0.561

Gnomad4 SAS AF: 0.296

Gnomad4 FIN AF: 0.248

Gnomad4 NFE AF: 0.185

Gnomad4 OTH AF: 0.260

Alfa AF: 0.217 Hom.: 1350

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

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

LitVar

Other links and lift over

dbSNP: rs2390639; hg19: chr2-169029764;