rs4986958

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_005534.4(IFNGR2):c.173C>G(p.Thr58Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0131 in 1,614,056 control chromosomes in the GnomAD database, including 912 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T58T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.046 ( 460 hom., cov: 32)

Exomes 𝑓: 0.0096 ( 452 hom. )

Consequence

IFNGR2
NM_005534.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.359

Publications

22 publications found

Variant links:

Genes affected

IFNGR2 (HGNC:5440): (interferon gamma receptor 2) This gene (IFNGR2) encodes the non-ligand-binding beta chain of the gamma interferon receptor. Human interferon-gamma receptor is a heterodimer of IFNGR1 and IFNGR2. Defects in IFNGR2 are a cause of mendelian susceptibility to mycobacterial disease (MSMD), also known as familial disseminated atypical mycobacterial infection. MSMD is a genetically heterogeneous disease with autosomal recessive, autosomal dominant or X-linked inheritance. [provided by RefSeq, Jul 2008]

IFNGR2 Gene-Disease associations (from GenCC):

immunodeficiency 28
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR2 deficiency
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
autosomal recessive Mendelian susceptibility to mycobacterial diseases due to complete IFNgammaR2 deficiency
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
autosomal recessive Mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR2 deficiency
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

IFNGR2 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=0.0018488467).

BP6

Variant 21-33414987-C-G is Benign according to our data. Variant chr21-33414987-C-G is described in ClinVar as Benign. ClinVar VariationId is 36376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNGR2	NM_005534.4 link	c.173C>G	p.Thr58Arg	missense_variant	Exon 2 of 7	ENST00000290219.11	NP_005525.2
IFNGR2	NM_001329128.2 link	c.230C>G	p.Thr77Arg	missense_variant	Exon 3 of 8		NP_001316057.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFNGR2	ENST00000290219.11 link	c.173C>G	p.Thr58Arg	missense_variant	Exon 2 of 7	1	NM_005534.4	ENSP00000290219.5		P38484

Frequencies

GnomAD3 genomes

AF:

0.0463

AC:

7039

AN:

152090

Hom.:

458

Cov.:

show subpopulations

Gnomad AFR

AF:

0.145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0292

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00613

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00595

Gnomad OTH

AF:

0.0425

GnomAD2 exomes

AF:

0.0155

AC:

3900

AN:

251482

AF XY:

0.0124

show subpopulations

Gnomad AFR exome

AF:

0.147

Gnomad AMR exome

AF:

0.0151

Gnomad ASJ exome

AF:

0.00784

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00564

Gnomad NFE exome

AF:

0.00555

Gnomad OTH exome

AF:

0.0138

GnomAD4 exome

AF:

0.00960

AC:

14039

AN:

1461848

Hom.:

452

Cov.:

AF XY:

0.00883

AC XY:

6425

AN XY:

727224

show subpopulations

African (AFR)

AF:

0.149

AC:

4983

AN:

33474

American (AMR)

AF:

0.0165

AC:

739

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00735

AC:

192

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00286

AC:

247

AN:

86258

European-Finnish (FIN)

AF:

0.00481

AC:

257

AN:

53418

Middle Eastern (MID)

AF:

0.0182

AC:

105

AN:

5768

European-Non Finnish (NFE)

AF:

0.00594

AC:

6610

AN:

1111974

Other (OTH)

AF:

0.0150

AC:

905

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

775

1551

2326

3102

3877

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

338

676

1014

1352

1690

<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:

0.0463

AC:

7043

AN:

152208

Hom.:

460

Cov.:

AF XY:

0.0451

AC XY:

3360

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.144

AC:

5988

AN:

41492

American (AMR)

AF:

0.0292

AC:

446

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0101

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00166

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00613

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00596

AC:

405

AN:

68008

Other (OTH)

AF:

0.0421

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

314

628

941

1255

1569

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

204

272

340

<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:

0.00769

Hom.:

Bravo

AF:

0.0525

TwinsUK

AF:

0.00755

AC:

ALSPAC

AF:

0.00701

AC:

ESP6500AA

AF:

0.145

AC:

637

ESP6500EA

AF:

0.00593

AC:

ExAC

AF:

0.0171

AC:

2081

Asia WGS

AF:

0.00635

AC:

AN:

3478

EpiCase

AF:

0.00578

EpiControl

AF:

0.00699

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 09, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Immunodeficiency 28

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Interferon gamma receptor deficiency

Benign:1

Aug 18, 2011

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing;curation

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.41

T;.

Eigen

Benign

-0.074

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.083

LIST_S2

Benign

0.71

T;T

MetaRNN

Benign

0.0018

T;T

MetaSVM

Benign

-0.88

MutationAssessor

Uncertain

2.7

M;.

PhyloP100

0.36

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-2.8

D;D

REVEL

Benign

0.24

Sift

Uncertain

0.019

D;D

Sift4G

Benign

0.13

T;T

Polyphen

0.88

P;P

Vest4

0.15

MPC

1.2

ClinPred

0.029

GERP RS

4.5

Varity_R

0.24

gMVP

0.35

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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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