rs7977692

Variant names:

• chr12-56341465-A-G
• rs7977692
• NM_005419.4:c.*1924T>C

Variant summary

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

The NM_005419.4(STAT2):​c.*1924T>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,194 control chromosomes in the GnomAD database, including 2,603 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 0.10 (2603 hom., cov: 31)
  • Exomes 𝑓: 0.017 (0 hom.)
• Consequence: STAT2 NM_005419.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.101

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAT2	NM_005419.4	c.*1924T>C		downstream_gene_variant		ENST00000314128.9	NP_005410.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAT2	ENST00000314128.9	c.*1924T>C		downstream_gene_variant		1	NM_005419.4	ENSP00000315768.4

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15442 AN: 152016 Hom.: 2587 Cov.: 31

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0469

Gnomad ASJ AF: 0.0216

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00191

Gnomad OTH AF: 0.0659

GnomAD4 exome AF: 0.0167 AC: 1 AN: 60 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 40

Gnomad4 AMR exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.102 AC: 15503 AN: 152134 Hom.: 2603 Cov.: 31 AF XY: 0.0985 AC XY: 7332 AN XY: 74416

Gnomad4 AFR AF: 0.348

Gnomad4 AMR AF: 0.0469

Gnomad4 ASJ AF: 0.0216

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00191

Gnomad4 OTH AF: 0.0652

Alfa AF: 0.0784 Hom.: 186

Bravo AF: 0.116

Asia WGS AF: 0.0200 AC: 71 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.7
DANN	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7977692; hg19: chr12-56735249;