2-168235432-A-C

Variant names:

• chr2-168235432-A-C
• rs2390669
• NM_013233.3:c.208+11796T>G

Variant summary

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

The NM_013233.3(STK39):​c.208+11796T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 144,606 control chromosomes in the GnomAD database, including 1,564 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 0.14 (1564 hom., cov: 30)
• Consequence: STK39 NM_013233.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.93
• Publications: 19 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK39	NM_013233.3	c.208+11796T>G		intron_variant	Intron 1 of 17	ENST00000355999.5	NP_037365.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK39	ENST00000355999.5	c.208+11796T>G		intron_variant	Intron 1 of 17	1	NM_013233.3	ENSP00000348278.4
STK39	ENST00000697205.1	c.208+11796T>G		intron_variant	Intron 1 of 16			ENSP00000513185.1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 20845 AN: 144524 Hom.: 1562 Cov.: 30

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.0946

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.156

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

GnomAD4 genome AF: 0.144 AC: 20858 AN: 144606 Hom.: 1564 Cov.: 30 AF XY: 0.144 AC XY: 10124 AN XY: 70376

African (AFR) AF: 0.119 AC: 4284 AN: 36072

American (AMR) AF: 0.198 AC: 2945 AN: 14868

Ashkenazi Jewish (ASJ) AF: 0.0946 AC: 325 AN: 3436

East Asian (EAS) AF: 0.326 AC: 1612 AN: 4952

South Asian (SAS) AF: 0.205 AC: 947 AN: 4610

European-Finnish (FIN) AF: 0.112 AC: 1133 AN: 10072

Middle Eastern (MID) AF: 0.224 AC: 65 AN: 290

European-Non Finnish (NFE) AF: 0.135 AC: 9098 AN: 67378

Other (OTH) AF: 0.159 AC: 321 AN: 2024

Alfa AF: 0.137 Hom.: 6071

Bravo AF: 0.144

Asia WGS AF: 0.228 AC: 793 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.1
DANN	Benign	0.56
PhyloP100		1.9
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: rs2390669; hg19: chr2-169091942;