2-168247286-C-CGCCGGG

Position:

• chr2-168247286-C-CGCCGGG

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP3 BP6_Moderate BA1

The NM_013233.3(STK39):​c.149_150insCCCGGC​(p.Pro49_Ala50dup) variant causes a 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 inframe_insertion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.92

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK39	NM_013233.3	c.149_150insCCCGGC	p.Pro49_Ala50dup	inframe_insertion	1/18	ENST00000355999.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK39	ENST00000355999.5	c.149_150insCCCGGC	p.Pro49_Ala50dup	inframe_insertion	1/18	1	NM_013233.3	P1
STK39	ENST00000697205.1	c.149_150insCCCGGC	p.Pro49_Ala50dup	inframe_insertion	1/17

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

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

Gnomad4 AFR exome AF: 0.246

Gnomad4 AMR exome AF: 0.216

Gnomad4 ASJ exome AF: 0.596

Gnomad4 EAS exome AF: 0.0837

Gnomad4 SAS exome AF: 0.531

Gnomad4 FIN exome AF: 0.322

Gnomad4 NFE exome AF: 0.717

Gnomad4 OTH exome AF: 0.608

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

Gnomad4 AFR AF: 0.311

Gnomad4 AMR AF: 0.451

Gnomad4 ASJ AF: 0.695

Gnomad4 EAS AF: 0.172

Gnomad4 SAS AF: 0.539

Gnomad4 FIN AF: 0.673

Gnomad4 NFE AF: 0.734

Gnomad4 OTH AF: 0.556

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 21, 2018

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs537577117; hg19: chr2-169103796;