21-33427043-C-G

Variant names:

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.561+11C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.729 in 1,605,584 control chromosomes in the GnomAD database, including 430,378 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.77 ( 45896 hom., cov: 29)

Exomes 𝑓: 0.72 ( 384482 hom. )

Consequence

IFNGR2
NM_005534.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.0310

Publications

19 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 (BayesDel_noAF=-0.87).

BP6

Variant 21-33427043-C-G is Benign according to our data. Variant chr21-33427043-C-G is described in ClinVar as Benign. ClinVar VariationId is 402963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.962 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNGR2	NM_005534.4 link	c.561+11C>G		intron_variant	Intron 4 of 6	ENST00000290219.11	NP_005525.2
IFNGR2	NM_001329128.2 link	c.618+11C>G		intron_variant	Intron 5 of 7		NP_001316057.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFNGR2	ENST00000290219.11 link	c.561+11C>G		intron_variant	Intron 4 of 6	1	NM_005534.4	ENSP00000290219.5		P38484

Frequencies

GnomAD3 genomes

AF:

0.773

AC:

117281

AN:

151802

Hom.:

45835

Cov.:

show subpopulations

Gnomad AFR

AF:

0.864

Gnomad AMI

AF:

0.626

Gnomad AMR

AF:

0.813

Gnomad ASJ

AF:

0.645

Gnomad EAS

AF:

0.985

Gnomad SAS

AF:

0.775

Gnomad FIN

AF:

0.798

Gnomad MID

AF:

0.690

Gnomad NFE

AF:

0.697

Gnomad OTH

AF:

0.743

GnomAD2 exomes

AF:

0.769

AC:

192779

AN:

250840

AF XY:

0.760

show subpopulations

Gnomad AFR exome

AF:

0.871

Gnomad AMR exome

AF:

0.859

Gnomad ASJ exome

AF:

0.641

Gnomad EAS exome

AF:

0.994

Gnomad FIN exome

AF:

0.800

Gnomad NFE exome

AF:

0.698

Gnomad OTH exome

AF:

0.730

GnomAD4 exome

AF:

0.724

AC:

1052300

AN:

1453664

Hom.:

384482

Cov.:

AF XY:

0.723

AC XY:

523217

AN XY:

723656

show subpopulations

African (AFR)

AF:

0.868

AC:

28895

AN:

33284

American (AMR)

AF:

0.852

AC:

38090

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.644

AC:

16790

AN:

26074

East Asian (EAS)

AF:

0.978

AC:

38815

AN:

39682

South Asian (SAS)

AF:

0.764

AC:

65726

AN:

86036

European-Finnish (FIN)

AF:

0.790

AC:

42175

AN:

53384

Middle Eastern (MID)

AF:

0.682

AC:

3917

AN:

5746

European-Non Finnish (NFE)

AF:

0.700

AC:

773721

AN:

1104692

Other (OTH)

AF:

0.735

AC:

44171

AN:

60082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

12745

25491

38236

50982

63727

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19612

39224

58836

78448

98060

<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:

0.773

AC:

117400

AN:

151920

Hom.:

45896

Cov.:

AF XY:

0.780

AC XY:

57878

AN XY:

74228

show subpopulations

African (AFR)

AF:

0.864

AC:

35824

AN:

41452

American (AMR)

AF:

0.814

AC:

12387

AN:

15220

Ashkenazi Jewish (ASJ)

AF:

0.645

AC:

2235

AN:

3464

East Asian (EAS)

AF:

0.985

AC:

5086

AN:

5166

South Asian (SAS)

AF:

0.774

AC:

3732

AN:

4820

European-Finnish (FIN)

AF:

0.798

AC:

8397

AN:

10522

Middle Eastern (MID)

AF:

0.697

AC:

205

AN:

294

European-Non Finnish (NFE)

AF:

0.697

AC:

47405

AN:

67976

Other (OTH)

AF:

0.744

AC:

1562

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1290

2581

3871

5162

6452

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

854

1708

2562

3416

4270

<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:

0.724

Hom.:

7369

Bravo

AF:

0.781

Asia WGS

AF:

0.890

AC:

3097

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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: Frequency -

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 92% of patients studied by a panel of primary immunodeficiencies. Number of patients: 81. Only high quality variants are reported. -

Immunodeficiency 28

Benign:2

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.65

(source)

DANN

Benign

0.51

PhyloP100

-0.031

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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