Variant rs2020854 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005419.4(STAT2):c.1257+6A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.087 in 1,613,970 control chromosomes in the GnomAD database, including 14,529 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 6143 hom., cov: 31)

Exomes 𝑓: 0.076 ( 8386 hom. )

Consequence

STAT2
NM_005419.4 splice_region, intron

Scores

Splicing: ADA: 0.000003225

Clinical Significance

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

Conservation

PhyloP100: -0.514

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:

STAT2 (HGNC:):

STAT2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 12-56349583-T-C is Benign according to our data. Variant chr12-56349583-T-C is described in ClinVar as [Benign]. Clinvar id is 1167213.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STAT2	NM_005419.4 linkuse as main transcript	c.1257+6A>G		splice_region_variant, intron_variant		ENST00000314128.9	NP_005410.1	P52630-3R9QE65

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STAT2	ENST00000314128.9 linkuse as main transcript	c.1257+6A>G		splice_region_variant, intron_variant		1	NM_005419.4	ENSP00000315768.4		P52630-3

Frequencies

GnomAD3 genomes

AF:

0.195

AC:

29663

AN:

151962

Hom.:

6111

Cov.:

show subpopulations

Gnomad AFR

AF:

0.526

Gnomad AMI

AF:

0.0493

Gnomad AMR

AF:

0.118

Gnomad ASJ

AF:

0.0429

Gnomad EAS

AF:

0.0347

Gnomad SAS

AF:

0.0212

Gnomad FIN

AF:

0.0539

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0710

Gnomad OTH

AF:

0.128

GnomAD3 exomes

AF:

0.0894

AC:

22474

AN:

251482

Hom.:

2801

AF XY:

0.0785

AC XY:

10669

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.536

Gnomad AMR exome

AF:

0.0821

Gnomad ASJ exome

AF:

0.0434

Gnomad EAS exome

AF:

0.0298

Gnomad SAS exome

AF:

0.0250

Gnomad FIN exome

AF:

0.0557

Gnomad NFE exome

AF:

0.0664

Gnomad OTH exome

AF:

0.0679

GnomAD4 exome

AF:

0.0757

AC:

110639

AN:

1461890

Hom.:

8386

Cov.:

AF XY:

0.0730

AC XY:

53104

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.539

Gnomad4 AMR exome

AF:

0.0858

Gnomad4 ASJ exome

AF:

0.0432

Gnomad4 EAS exome

AF:

0.0365

Gnomad4 SAS exome

AF:

0.0234

Gnomad4 FIN exome

AF:

0.0547

Gnomad4 NFE exome

AF:

0.0678

Gnomad4 OTH exome

AF:

0.0907

GnomAD4 genome

AF:

0.196

AC:

29758

AN:

152080

Hom.:

6143

Cov.:

AF XY:

0.189

AC XY:

14049

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.526

Gnomad4 AMR

AF:

0.118

Gnomad4 ASJ

AF:

0.0429

Gnomad4 EAS

AF:

0.0346

Gnomad4 SAS

AF:

0.0210

Gnomad4 FIN

AF:

0.0539

Gnomad4 NFE

AF:

0.0710

Gnomad4 OTH

AF:

0.131

Alfa

AF:

0.0952

Hom.:

2135

Bravo

AF:

0.213

Asia WGS

AF:

0.104

AC:

361

AN:

3478

EpiCase

AF:

0.0647

EpiControl

AF:

0.0612

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

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.7

DANN

Benign

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0000032

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.050

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