2-168184876-T-G

Variant names:

• chr2-168184876-T-G
• rs6749447
• NM_013233.3:c.209-2786A>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.209-2786A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 152,108 control chromosomes in the GnomAD database, including 11,460 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 0.37 (11460 hom., cov: 32)
• Consequence: STK39 NM_013233.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0220
• Publications: 61 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013233.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK39	NM_013233.3	MANE Select	c.209-2786A>C		intron	N/A	NP_037365.2	Q9UEW8-1
	STK39	NM_001410961.1		c.209-2786A>C		intron	N/A	NP_001397890.1	A0A8V8TKT5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK39	ENST00000355999.5	TSL:1 MANE Select	c.209-2786A>C		intron	N/A	ENSP00000348278.4	Q9UEW8-1
	STK39	ENST00000952313.1		c.209-2786A>C		intron	N/A	ENSP00000622372.1
	STK39	ENST00000697205.1		c.209-2786A>C		intron	N/A	ENSP00000513185.1	A0A8V8TKT5

Frequencies

GnomAD3 genomes AF: 0.369 AC: 56119 AN: 151992 Hom.: 11445 Cov.: 32

Gnomad AFR AF: 0.502

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.692

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.381

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

GnomAD4 genome AF: 0.369 AC: 56189 AN: 152108 Hom.: 11460 Cov.: 32 AF XY: 0.374 AC XY: 27820 AN XY: 74344

African (AFR) AF: 0.502 AC: 20838 AN: 41496

American (AMR) AF: 0.428 AC: 6543 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 918 AN: 3470

East Asian (EAS) AF: 0.693 AC: 3583 AN: 5168

South Asian (SAS) AF: 0.411 AC: 1982 AN: 4826

European-Finnish (FIN) AF: 0.302 AC: 3193 AN: 10562

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.265 AC: 18020 AN: 67988

Other (OTH) AF: 0.384 AC: 813 AN: 2116

Alfa AF: 0.310 Hom.: 15694

Bravo AF: 0.388

Asia WGS AF: 0.565 AC: 1963 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	13
DANN	Benign	0.77
PhyloP100		0.022
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: rs6749447; hg19: chr2-169041386;