21-33403590-TCGCCGCCGCCGC-TCGC

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4

The NM_005534.4(IFNGR2):c.54_62delCGCCGCCGC(p.Ala19_Ala21del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00005 in 1,219,792 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000050 ( 0 hom. )

Consequence

IFNGR2
NM_005534.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.20

Publications

2 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: Uncertain_significance. The variant received 2 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_005534.4.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005534.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNGR2	NM_005534.4	MANE Select	c.54_62delCGCCGCCGC	p.Ala19_Ala21del	disruptive_inframe_deletion	Exon 1 of 7	NP_005525.2
	IFNGR2	NM_001329128.2		c.54_62delCGCCGCCGC	p.Ala19_Ala21del	disruptive_inframe_deletion	Exon 1 of 8	NP_001316057.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
IFNGR2	ENST00000290219.11	TSL:1 MANE Select	c.54_62delCGCCGCCGC	p.Ala19_Ala21del	disruptive_inframe_deletion	Exon 1 of 7	ENSP00000290219.5
IFNGR2	ENST00000381995.5	TSL:5	c.54_62delCGCCGCCGC	p.Ala19_Ala21del	disruptive_inframe_deletion	Exon 1 of 8	ENSP00000371425.1
IFNGR2	ENST00000439213.5	TSL:5	n.54_62delCGCCGCCGC		non_coding_transcript_exon	Exon 1 of 7	ENSP00000407541.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000500

AC:

AN:

1219792

Hom.:

AF XY:

0.0000568

AC XY:

AN XY:

598222

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24578

American (AMR)

AF:

0.00

AC:

AN:

18944

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19830

East Asian (EAS)

AF:

0.00

AC:

AN:

26094

South Asian (SAS)

AF:

0.00

AC:

AN:

57392

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28774

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3450

European-Non Finnish (NFE)

AF:

0.0000615

AC:

AN:

991578

Other (OTH)

AF:

0.00

AC:

AN:

49152

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.440

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Immunodeficiency 28

Uncertain:1

Mar 12, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with IFNGR2-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant, c.54_62del, results in the deletion of 3 amino acid(s) of the IFNGR2 protein (p.Ala20_Ala22del), but otherwise preserves the integrity of the reading frame.

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.2

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over