chr12-56344189-A-G

Position:

• chr12-56344189-A-G

Variant summary

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

The NM_005419.4(STAT2):​c.2103-54T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0877 in 1,510,784 control chromosomes in the GnomAD database, including 13,976 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 0.20 (6199 hom., cov: 32)
  • Exomes 𝑓: 0.076 (7777 hom.)
• Consequence: STAT2 NM_005419.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0850

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STAT2	NM_005419.4	c.2103-54T>C		intron_variant		ENST00000314128.9	NP_005410.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STAT2	ENST00000314128.9	c.2103-54T>C		intron_variant		1	NM_005419.4	ENSP00000315768	P2

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29768 AN: 152072 Hom.: 6166 Cov.: 32

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.0495

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.0424

Gnomad EAS AF: 0.0346

Gnomad SAS AF: 0.0209

Gnomad FIN AF: 0.0538

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0709

Gnomad OTH AF: 0.126

GnomAD4 exome AF: 0.0756 AC: 102685 AN: 1358594 Hom.: 7777 AF XY: 0.0732 AC XY: 48634 AN XY: 664544

Gnomad4 AFR exome AF: 0.542

Gnomad4 AMR exome AF: 0.0879

Gnomad4 ASJ exome AF: 0.0424

Gnomad4 EAS exome AF: 0.0367

Gnomad4 SAS exome AF: 0.0231

Gnomad4 FIN exome AF: 0.0542

Gnomad4 NFE exome AF: 0.0677

Gnomad4 OTH exome AF: 0.0911

GnomAD4 genome AF: 0.196 AC: 29864 AN: 152190 Hom.: 6199 Cov.: 32 AF XY: 0.190 AC XY: 14104 AN XY: 74398

Gnomad4 AFR AF: 0.528

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.0424

Gnomad4 EAS AF: 0.0345

Gnomad4 SAS AF: 0.0209

Gnomad4 FIN AF: 0.0538

Gnomad4 NFE AF: 0.0709

Gnomad4 OTH AF: 0.130

Alfa AF: 0.0807 Hom.: 2251

Bravo AF: 0.214

Asia WGS AF: 0.105 AC: 366 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.6
DANN	Benign	0.40

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: rs2066808; hg19: chr12-56737973;