2-168247349-C-G

Position:

• chr2-168247349-C-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_013233.3(STK39):​c.87G>C​(p.Ala29=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0026 in 1,049,268 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (32 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (16 hom.)
• Consequence: STK39 NM_013233.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.490

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 2-168247349-C-G is Benign according to our data. Variant chr2-168247349-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 786488.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.49 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0117 (1711/146694) while in subpopulation AFR AF= 0.0398 (1632/40970). AF 95% confidence interval is 0.0382. There are 32 homozygotes in gnomad4. There are 832 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1711 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK39	NM_013233.3	c.87G>C	p.Ala29=	synonymous_variant	1/18	ENST00000355999.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK39	ENST00000355999.5	c.87G>C	p.Ala29=	synonymous_variant	1/18	1	NM_013233.3	P1
STK39	ENST00000697205.1	c.87G>C	p.Ala29=	synonymous_variant	1/17

Frequencies

GnomAD3 genomes AF: 0.0117 AC: 1709 AN: 146588 Hom.: 33 Cov.: 32

Gnomad AFR AF: 0.0399

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00331

Gnomad ASJ AF: 0.000589

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000106

Gnomad OTH AF: 0.0104

GnomAD4 exome AF: 0.00112 AC: 1015 AN: 902574 Hom.: 16 Cov.: 29 AF XY: 0.00106 AC XY: 446 AN XY: 421628

Gnomad4 AFR exome AF: 0.0443

Gnomad4 AMR exome AF: 0.00329

Gnomad4 ASJ exome AF: 0.000270

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000557

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000157

Gnomad4 OTH exome AF: 0.00259

GnomAD4 genome AF: 0.0117 AC: 1711 AN: 146694 Hom.: 32 Cov.: 32 AF XY: 0.0116 AC XY: 832 AN XY: 71436

Gnomad4 AFR AF: 0.0398

Gnomad4 AMR AF: 0.00331

Gnomad4 ASJ AF: 0.000589

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000106

Gnomad4 OTH AF: 0.0103

Alfa AF: 0.00895 Hom.: 3

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 24, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	8.4
DANN	Benign	0.53

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: rs576855530; hg19: chr2-169103859;