2-168247286-C-CGCCGGG

Variant names:

• chr2-168247286-C-CGCCGGG
• rs537577117
• NM_013233.3:c.144_149dupCCCGGC

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP3 BP6_Moderate BA1

The NM_013233.3(STK39):​c.144_149dupCCCGGC​(p.Ala50_Ala51insProAla) variant causes a disruptive inframe insertion change. The variant allele was found at a frequency of 0.667 in 1,006,450 control chromosomes in the GnomAD database, including 245,814 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.55 (24816 hom., cov: 0)
  • Exomes 𝑓: 0.69 (220998 hom.)
• Consequence: STK39 NM_013233.3 disruptive_inframe_insertion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.92
• 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 -11 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_013233.3
• BP6: Variant 2-168247286-C-CGCCGGG is Benign according to our data. Variant chr2-168247286-C-CGCCGGG is described in ClinVar as Benign. ClinVar VariationId is 769262.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.728 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.144_149dupCCCGGC	p.Ala50_Ala51insProAla	disruptive_inframe_insertion	Exon 1 of 18	NP_037365.2	Q9UEW8-1
	STK39	NM_001410961.1		c.144_149dupCCCGGC	p.Ala50_Ala51insProAla	disruptive_inframe_insertion	Exon 1 of 17	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.144_149dupCCCGGC	p.Ala50_Ala51insProAla	disruptive_inframe_insertion	Exon 1 of 18	ENSP00000348278.4	Q9UEW8-1
	STK39	ENST00000952313.1		c.144_149dupCCCGGC	p.Ala50_Ala51insProAla	disruptive_inframe_insertion	Exon 1 of 19	ENSP00000622372.1
	STK39	ENST00000697205.1		c.144_149dupCCCGGC	p.Ala50_Ala51insProAla	disruptive_inframe_insertion	Exon 1 of 17	ENSP00000513185.1	A0A8V8TKT5

Frequencies

GnomAD3 genomes AF: 0.555 AC: 79515 AN: 143340 Hom.: 24828 Cov.: 0

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.695

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.734

Gnomad OTH AF: 0.562

GnomAD2 exomes AF: 0.00 AC: 0 AN: 6 AF XY: 0.00

Gnomad FIN exome AF: 0.00

GnomAD4 exome AF: 0.685 AC: 591424 AN: 863006 Hom.: 220998 Cov.: 35 AF XY: 0.684 AC XY: 275045 AN XY: 401856

African (AFR) AF: 0.246 AC: 4358 AN: 17702

American (AMR) AF: 0.216 AC: 644 AN: 2986

Ashkenazi Jewish (ASJ) AF: 0.596 AC: 3815 AN: 6402

East Asian (EAS) AF: 0.0837 AC: 1140 AN: 13618

South Asian (SAS) AF: 0.531 AC: 9304 AN: 17510

European-Finnish (FIN) AF: 0.322 AC: 1284 AN: 3990

Middle Eastern (MID) AF: 0.574 AC: 1049 AN: 1828

European-Non Finnish (NFE) AF: 0.717 AC: 551731 AN: 769210

Other (OTH) AF: 0.608 AC: 18099 AN: 29760

GnomAD4 genome AF: 0.554 AC: 79509 AN: 143444 Hom.: 24816 Cov.: 0 AF XY: 0.549 AC XY: 38219 AN XY: 69652

African (AFR) AF: 0.311 AC: 12518 AN: 40238

American (AMR) AF: 0.451 AC: 6568 AN: 14568

Ashkenazi Jewish (ASJ) AF: 0.695 AC: 2327 AN: 3348

East Asian (EAS) AF: 0.172 AC: 835 AN: 4864

South Asian (SAS) AF: 0.539 AC: 2531 AN: 4698

European-Finnish (FIN) AF: 0.673 AC: 5346 AN: 7940

Middle Eastern (MID) AF: 0.557 AC: 157 AN: 282

European-Non Finnish (NFE) AF: 0.734 AC: 47401 AN: 64620

Other (OTH) AF: 0.556 AC: 1113 AN: 2000

Alfa AF: 0.458 Hom.: 1137

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.9
Mutation Taster		=78/22	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs537577117; hg19: chr2-169103796; COSMIC: COSV63598128;