rs2834213

Variant names:

• chr21-33420603-A-G
• rs2834213
• NM_005534.4:c.207-877A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005534.4(IFNGR2):​c.207-877A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 152,250 control chromosomes in the GnomAD database, including 3,318 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.19 (3318 hom., cov: 32)
• Consequence: IFNGR2 NM_005534.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.952
• Publications: 24 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNGR2	NM_005534.4	MANE Select	c.207-877A>G		intron	N/A	NP_005525.2
	IFNGR2	NM_001329128.2		c.264-877A>G		intron	N/A	NP_001316057.1	E7EUY1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNGR2	ENST00000290219.11	TSL:1 MANE Select	c.207-877A>G		intron	N/A	ENSP00000290219.5	P38484
	IFNGR2	ENST00000964420.1		c.264-877A>G		intron	N/A	ENSP00000634479.1
	IFNGR2	ENST00000897490.1		c.207-877A>G		intron	N/A	ENSP00000567549.1

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28837 AN: 152132 Hom.: 3314 Cov.: 32

Gnomad AFR AF: 0.0531

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.217

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.190 AC: 28854 AN: 152250 Hom.: 3318 Cov.: 32 AF XY: 0.194 AC XY: 14474 AN XY: 74426

African (AFR) AF: 0.0529 AC: 2201 AN: 41574

American (AMR) AF: 0.236 AC: 3605 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 686 AN: 3470

East Asian (EAS) AF: 0.159 AC: 824 AN: 5186

South Asian (SAS) AF: 0.201 AC: 972 AN: 4834

European-Finnish (FIN) AF: 0.296 AC: 3133 AN: 10586

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.245 AC: 16669 AN: 68014

Other (OTH) AF: 0.216 AC: 457 AN: 2112

Alfa AF: 0.225 Hom.: 3384

Bravo AF: 0.179

Asia WGS AF: 0.188 AC: 654 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.24
DANN	Benign	0.64
PhyloP100		-0.95
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2834213; hg19: chr21-34792910;