rs2031237

Positions:

• chr13-98457065-C-A
• chr13-98457065-C-T

Variant summary

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

The NM_001032296.4(STK24):​c.1259+103G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 1,398,436 control chromosomes in the GnomAD database, including 54,866 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 0.26 (5223 hom., cov: 33)
  • Exomes 𝑓: 0.28 (49643 hom.)
• Consequence: STK24 NM_001032296.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.409

Genes affected

STK24 (HGNC:11403): (serine/threonine kinase 24) This gene encodes a serine/threonine protein kinase that functions upstream of mitogen-activated protein kinase (MAPK) signaling. The encoded protein is cleaved into two chains by caspases; the N-terminal fragment (MST3/N) translocates to the nucleus and promotes programmed cells death. There is a pseudogene for this gene on chromosome X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK24	NM_001032296.4	c.1259+103G>T		intron_variant		ENST00000539966.6
STK24	NM_001286649.2	c.1202+103G>T		intron_variant
STK24	NM_003576.5	c.1295+103G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK24	ENST00000539966.6	c.1259+103G>T		intron_variant		1	NM_001032296.4	P1

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39237 AN: 151982 Hom.: 5209 Cov.: 33

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.252

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.258

GnomAD4 exome AF: 0.279 AC: 347529 AN: 1246334 Hom.: 49643 Cov.: 18 AF XY: 0.278 AC XY: 170037 AN XY: 612578

Gnomad4 AFR exome AF: 0.224

Gnomad4 AMR exome AF: 0.223

Gnomad4 ASJ exome AF: 0.262

Gnomad4 EAS exome AF: 0.144

Gnomad4 SAS exome AF: 0.229

Gnomad4 FIN exome AF: 0.249

Gnomad4 NFE exome AF: 0.293

Gnomad4 OTH exome AF: 0.263

GnomAD4 genome AF: 0.258 AC: 39282 AN: 152102 Hom.: 5223 Cov.: 33 AF XY: 0.254 AC XY: 18851 AN XY: 74344

Gnomad4 AFR AF: 0.228

Gnomad4 AMR AF: 0.241

Gnomad4 ASJ AF: 0.257

Gnomad4 EAS AF: 0.154

Gnomad4 SAS AF: 0.213

Gnomad4 FIN AF: 0.226

Gnomad4 NFE AF: 0.296

Gnomad4 OTH AF: 0.257

Alfa AF: 0.197 Hom.: 250

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.4
DANN	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs2031237; hg19: chr13-99109319;