2-168182743-G-C

Variant names:

• chr2-168182743-G-C
• rs12692877
• NM_013233.3:c.209-653C>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_013233.3(STK39):​c.209-653C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 152,062 control chromosomes in the GnomAD database, including 7,940 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 0.32 (7940 hom., cov: 33)
• Consequence: STK39 NM_013233.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.766
• Publications: 3 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.444 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK39	NM_013233.3	MANE Select	c.209-653C>G		intron	N/A	NP_037365.2
	STK39	NM_001410961.1		c.209-653C>G		intron	N/A	NP_001397890.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK39	ENST00000355999.5	TSL:1 MANE Select	c.209-653C>G		intron	N/A	ENSP00000348278.4
	STK39	ENST00000697205.1		c.209-653C>G		intron	N/A	ENSP00000513185.1

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48352 AN: 151944 Hom.: 7933 Cov.: 33

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.318 AC: 48382 AN: 152062 Hom.: 7940 Cov.: 33 AF XY: 0.323 AC XY: 24019 AN XY: 74356

African (AFR) AF: 0.371 AC: 15392 AN: 41464

American (AMR) AF: 0.392 AC: 5994 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 818 AN: 3470

East Asian (EAS) AF: 0.460 AC: 2376 AN: 5168

South Asian (SAS) AF: 0.375 AC: 1808 AN: 4822

European-Finnish (FIN) AF: 0.308 AC: 3256 AN: 10570

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.261 AC: 17744 AN: 67976

Other (OTH) AF: 0.333 AC: 703 AN: 2110

Alfa AF: 0.161 Hom.: 295

Bravo AF: 0.327

Asia WGS AF: 0.430 AC: 1495 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	13
DANN	Benign	0.50
PhyloP100		0.77
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: rs12692877; hg19: chr2-169039253;