rs2268241

Positions:

• chr21-33408744-G-A
• chrNW_003315970.2-3316-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005534.4(IFNGR2):​c.73+5128G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,080 control chromosomes in the GnomAD database, including 4,463 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 0.21 (4463 hom., cov: 32)
• Consequence: IFNGR2 NM_005534.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.698

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFNGR2	NM_005534.4	c.73+5128G>A		intron_variant		ENST00000290219.11
IFNGR2	NM_001329128.2	c.74-2092G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFNGR2	ENST00000290219.11	c.73+5128G>A		intron_variant		1	NM_005534.4	P1

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32635 AN: 151962 Hom.: 4456 Cov.: 32

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.215 AC: 32663 AN: 152080 Hom.: 4463 Cov.: 32 AF XY: 0.216 AC XY: 16093 AN XY: 74344

Gnomad4 AFR AF: 0.350

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.144

Gnomad4 EAS AF: 0.425

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.131

Gnomad4 OTH AF: 0.174

Alfa AF: 0.140 Hom.: 1256

Bravo AF: 0.222

Asia WGS AF: 0.385 AC: 1335 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.35
DANN	Benign	0.20

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

LitVar

Other links and lift over

dbSNP: rs2268241; hg19: chr21-34781050;