2-168227647-G-A

Position:

• chr2-168227647-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013233.3(STK39):​c.208+19581C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 151,996 control chromosomes in the GnomAD database, including 12,098 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 0.38 (12098 hom., cov: 32)
• Consequence: STK39 NM_013233.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.223

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK39	NM_013233.3	c.208+19581C>T		intron_variant		ENST00000355999.5	NP_037365.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK39	ENST00000355999.5	c.208+19581C>T		intron_variant		1	NM_013233.3	ENSP00000348278	P1
STK39	ENST00000697205.1	c.208+19581C>T		intron_variant				ENSP00000513185

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58298 AN: 151878 Hom.: 12094 Cov.: 32

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.403

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

GnomAD4 genome AF: 0.384 AC: 58322 AN: 151996 Hom.: 12098 Cov.: 32 AF XY: 0.379 AC XY: 28139 AN XY: 74278

Gnomad4 AFR AF: 0.270

Gnomad4 AMR AF: 0.308

Gnomad4 ASJ AF: 0.456

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.356

Gnomad4 FIN AF: 0.416

Gnomad4 NFE AF: 0.481

Gnomad4 OTH AF: 0.400

Alfa AF: 0.408 Hom.: 2237

Bravo AF: 0.368

Asia WGS AF: 0.255 AC: 888 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	14
DANN	Benign	0.69

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: rs1356373; hg19: chr2-169084157;