rs61754171

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_005419.4(STAT2):c.2472T>C(p.Ala824Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0184 in 1,614,186 control chromosomes in the GnomAD database, including 366 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 32 hom., cov: 32)

Exomes 𝑓: 0.019 ( 334 hom. )

Consequence

STAT2
NM_005419.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0190

Variant links:

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]

STAT2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 12-56343473-A-G is Benign according to our data. Variant chr12-56343473-A-G is described in ClinVar as [Benign]. Clinvar id is 403492.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.019 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0149 (2272/152336) while in subpopulation NFE AF= 0.0208 (1417/68020). AF 95% confidence interval is 0.0199. There are 32 homozygotes in gnomad4. There are 1199 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 32 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAT2	NM_005419.4 link	c.2472T>C	p.Ala824Ala	synonymous_variant	Exon 24 of 24	ENST00000314128.9	NP_005410.1	P52630-3R9QE65

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAT2	ENST00000314128.9 link	c.2472T>C	p.Ala824Ala	synonymous_variant	Exon 24 of 24	1	NM_005419.4	ENSP00000315768.4		P52630-3

Frequencies

GnomAD3 genomes

AF:

0.0149

AC:

2271

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00292

Gnomad AMI

AF:

0.0241

Gnomad AMR

AF:

0.00537

Gnomad ASJ

AF:

0.00606

Gnomad EAS

AF:

0.000576

Gnomad SAS

AF:

0.0176

Gnomad FIN

AF:

0.0466

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0208

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.0162

AC:

4082

AN:

251412

Hom.:

AF XY:

0.0168

AC XY:

2287

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.00277

Gnomad AMR exome

AF:

0.00286

Gnomad ASJ exome

AF:

0.00714

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0181

Gnomad FIN exome

AF:

0.0422

Gnomad NFE exome

AF:

0.0204

Gnomad OTH exome

AF:

0.0130

GnomAD4 exome

AF:

0.0187

AC:

27399

AN:

1461850

Hom.:

334

Cov.:

AF XY:

0.0188

AC XY:

13657

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.00212

Gnomad4 AMR exome

AF:

0.00284

Gnomad4 ASJ exome

AF:

0.00662

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0194

Gnomad4 FIN exome

AF:

0.0407

Gnomad4 NFE exome

AF:

0.0199

Gnomad4 OTH exome

AF:

0.0166

GnomAD4 genome

AF:

0.0149

AC:

2272

AN:

152336

Hom.:

Cov.:

AF XY:

0.0161

AC XY:

1199

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.00291

Gnomad4 AMR

AF:

0.00536

Gnomad4 ASJ

AF:

0.00606

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.0178

Gnomad4 FIN

AF:

0.0466

Gnomad4 NFE

AF:

0.0208

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.0178

Hom.:

Bravo

AF:

0.0109

Asia WGS

AF:

0.00779

AC:

AN:

3478

EpiCase

AF:

0.0161

EpiControl

AF:

0.0170

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection

Benign:1

Jan 01, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: In cis with c.2473G>T variant (per exac) -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

3.8

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over