rs2066819

Positions:

• chr12-56356420-C-T

Variant summary

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

The NM_005419.4(STAT2):​c.131+21G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0581 in 1,610,634 control chromosomes in the GnomAD database, including 3,110 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 0.046 (222 hom., cov: 31)
  • Exomes 𝑓: 0.059 (2888 hom.)
• Consequence: STAT2 NM_005419.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.805

Genes affected

STAT2 (HGNC:11363): (signal transducer and activator of transcription 2) The protein encoded by this gene is a member of the STAT protein family. In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and then form homo- or heterodimers that translocate to the cell nucleus where they act as transcription activators. In response to interferon (IFN), this protein forms a complex with STAT1 and IFN regulatory factor family protein p48 (ISGF3G), in which this protein acts as a transactivator, but lacks the ability to bind DNA directly. The protein mediates innate antiviral activity. Mutations in this gene result in Immunodeficiency 44. [provided by RefSeq, Aug 2020]

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 = 0.0667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAT2	NM_005419.4	c.131+21G>A		intron_variant		ENST00000314128.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAT2	ENST00000314128.9	c.131+21G>A		intron_variant		1	NM_005419.4	P2

Frequencies

GnomAD3 genomes AF: 0.0456 AC: 6935 AN: 152144 Hom.: 219 Cov.: 31

Gnomad AFR AF: 0.0110

Gnomad AMI AF: 0.0473

Gnomad AMR AF: 0.0530

Gnomad ASJ AF: 0.0202

Gnomad EAS AF: 0.0341

Gnomad SAS AF: 0.0194

Gnomad FIN AF: 0.0536

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0683

Gnomad OTH AF: 0.0291

GnomAD3 exomes AF: 0.0488 AC: 12168 AN: 249138 Hom.: 353 AF XY: 0.0484 AC XY: 6514 AN XY: 134636

Gnomad AFR exome AF: 0.00912

Gnomad AMR exome AF: 0.0536

Gnomad ASJ exome AF: 0.0236

Gnomad EAS exome AF: 0.0293

Gnomad SAS exome AF: 0.0238

Gnomad FIN exome AF: 0.0556

Gnomad NFE exome AF: 0.0642

Gnomad OTH exome AF: 0.0441

GnomAD4 exome AF: 0.0594 AC: 86611 AN: 1458372 Hom.: 2888 Cov.: 32 AF XY: 0.0589 AC XY: 42712 AN XY: 725232

Gnomad4 AFR exome AF: 0.00816

Gnomad4 AMR exome AF: 0.0531

Gnomad4 ASJ exome AF: 0.0242

Gnomad4 EAS exome AF: 0.0363

Gnomad4 SAS exome AF: 0.0223

Gnomad4 FIN exome AF: 0.0546

Gnomad4 NFE exome AF: 0.0664

Gnomad4 OTH exome AF: 0.0536

GnomAD4 genome AF: 0.0456 AC: 6947 AN: 152262 Hom.: 222 Cov.: 31 AF XY: 0.0446 AC XY: 3320 AN XY: 74450

Gnomad4 AFR AF: 0.0109

Gnomad4 AMR AF: 0.0530

Gnomad4 ASJ AF: 0.0202

Gnomad4 EAS AF: 0.0339

Gnomad4 SAS AF: 0.0199

Gnomad4 FIN AF: 0.0536

Gnomad4 NFE AF: 0.0684

Gnomad4 OTH AF: 0.0336

Alfa AF: 0.0535 Hom.: 61

Bravo AF: 0.0421

Asia WGS AF: 0.0670 AC: 231 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	3.9
DANN	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs2066819; hg19: chr12-56750204; COSMIC: COSV58477649; COSMIC: COSV58477649;