rs2066811

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005419.4(STAT2):c.1390A>G(p.Ile464Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0117 in 1,614,020 control chromosomes in the GnomAD database, including 1,543 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.060 ( 811 hom., cov: 31)

Exomes 𝑓: 0.0068 ( 732 hom. )

Consequence

STAT2
NM_005419.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.190

Publications

19 publications found

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 Gene-Disease associations (from GenCC):

primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection
Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P
pseudo-TORCH syndrome 3
Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)

STAT2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015448928).

BP6

Variant 12-56349213-T-C is Benign according to our data. Variant chr12-56349213-T-C is described in ClinVar as Benign. ClinVar VariationId is 475689.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAT2	NM_005419.4 link	c.1390A>G	p.Ile464Val	missense_variant	Exon 16 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.1390A>G	p.Ile464Val	missense_variant	Exon 16 of 24	1	NM_005419.4	ENSP00000315768.4		P52630-3

Frequencies

GnomAD3 genomes

AF:

0.0596

AC:

9056

AN:

152010

Hom.:

810

Cov.:

show subpopulations

Gnomad AFR

AF:

0.201

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0333

Gnomad ASJ

AF:

0.0133

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00150

Gnomad OTH

AF:

0.0397

GnomAD2 exomes

AF:

0.0169

AC:

4251

AN:

251478

AF XY:

0.0128

show subpopulations

Gnomad AFR exome

AF:

0.204

Gnomad AMR exome

AF:

0.0159

Gnomad ASJ exome

AF:

0.0148

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00131

Gnomad OTH exome

AF:

0.0119

GnomAD4 exome

AF:

0.00676

AC:

9879

AN:

1461892

Hom.:

732

Cov.:

AF XY:

0.00590

AC XY:

4293

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.201

AC:

6742

AN:

33480

American (AMR)

AF:

0.0170

AC:

759

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0137

AC:

358

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.000383

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.0114

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000897

AC:

998

AN:

1112010

Other (OTH)

AF:

0.0152

AC:

921

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

574

1149

1723

2298

2872

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

214

428

642

856

1070

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0596

AC:

9062

AN:

152128

Hom.:

811

Cov.:

AF XY:

0.0578

AC XY:

4300

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.200

AC:

8316

AN:

41478

American (AMR)

AF:

0.0333

AC:

509

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0133

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.000623

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00150

AC:

102

AN:

67982

Other (OTH)

AF:

0.0393

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

364

728

1093

1457

1821

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

252

336

420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0230

Hom.:

604

Bravo

AF:

0.0683

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.201

AC:

885

ESP6500EA

AF:

0.00209

AC:

ExAC

AF:

0.0200

AC:

2429

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.00169

EpiControl

AF:

0.00243

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.44

CADD

Benign

1.4

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.25

T;.

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.32

T;T

MetaRNN

Benign

0.0015

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

L;.

PhyloP100

0.19

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.060

N;N

REVEL

Benign

0.13

Sift

Benign

0.80

T;T

Sift4G

Benign

0.94

T;T

Polyphen

0.16

B;.

Vest4

0.030

MPC

0.34

ClinPred

0.0044

GERP RS

2.9

Varity_R

0.035

gMVP

0.52

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over