dbSNP rs753866192: IFNGR2:p.Leu13del (chr21-33403566-CGCT-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BS1

The NM_005534.4(IFNGR2):c.36_38delGCT(p.Leu13del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000101 in 1,214,354 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00010 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

IFNGR2
NM_005534.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.209

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BS1

Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.000101 (123/1214354) while in subpopulation SAS AF= 0.000383 (22/57448). AF 95% confidence interval is 0.000259. There are 0 homozygotes in gnomad4_exome. There are 65 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNGR2	NM_005534.4 link	c.36_38delGCT	p.Leu13del	disruptive_inframe_deletion	Exon 1 of 7	ENST00000290219.11	NP_005525.2
IFNGR2	NM_001329128.2 link	c.36_38delGCT	p.Leu13del	disruptive_inframe_deletion	Exon 1 of 8		NP_001316057.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFNGR2	ENST00000290219.11 link	c.36_38delGCT	p.Leu13del	disruptive_inframe_deletion	Exon 1 of 7	1	NM_005534.4	ENSP00000290219.5		P38484

Frequencies

GnomAD3 genomes

AF:

0.00000663

AC:

AN:

150806

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000660

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000444

AC:

AN:

60758

Hom.:

AF XY:

0.000363

AC XY:

AN XY:

35838

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000455

Gnomad ASJ exome

AF:

0.000525

Gnomad EAS exome

AF:

0.000852

Gnomad SAS exome

AF:

0.000421

Gnomad FIN exome

AF:

0.000765

Gnomad NFE exome

AF:

0.000406

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000101

AC:

123

AN:

1214354

Hom.:

AF XY:

0.000109

AC XY:

AN XY:

595824

show subpopulations

Gnomad4 AFR exome

AF:

0.000365

Gnomad4 AMR exome

AF:

0.000344

Gnomad4 ASJ exome

AF:

0.000303

Gnomad4 EAS exome

AF:

0.0000790

Gnomad4 SAS exome

AF:

0.000383

Gnomad4 FIN exome

AF:

0.000420

Gnomad4 NFE exome

AF:

0.0000608

Gnomad4 OTH exome

AF:

0.000103

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000663

AC:

AN:

150806

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73620

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000660

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over