Variant chr21-33403590-TCGC-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 3P and 5B. PM2PM4_SupportingBP6BS1

The NM_005534.4(IFNGR2):c.60_62delCGC(p.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 0.000703 in 1,211,410 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00070 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

IFNGR2
NM_005534.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.411

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;

PM4

Nonframeshift variant in NON repetitive region in NM_005534.4. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant 21-33403590-TCGC-T is Benign according to our data. Variant chr21-33403590-TCGC-T is described in ClinVar as [Likely_benign]. Clinvar id is 3350397.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.000703 (852/1211410) while in subpopulation SAS AF= 0.0034 (190/55814). AF 95% confidence interval is 0.00301. There are 0 homozygotes in gnomad4_exome. There are 482 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.60_62delCGC	p.Ala21del	disruptive_inframe_deletion	Exon 1 of 7	ENST00000290219.11	NP_005525.2
IFNGR2	NM_001329128.2 link	c.60_62delCGC	p.Ala21del	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.60_62delCGC	p.Ala21del	disruptive_inframe_deletion	Exon 1 of 7	1	NM_005534.4	ENSP00000290219.5		P38484

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

150188

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000661

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:

0.00347

AC:

175

AN:

50422

Hom.:

AF XY:

0.00313

AC XY:

AN XY:

30078

show subpopulations

Gnomad AFR exome

AF:

0.00836

Gnomad AMR exome

AF:

0.00304

Gnomad ASJ exome

AF:

0.00272

Gnomad EAS exome

AF:

0.00552

Gnomad SAS exome

AF:

0.00337

Gnomad FIN exome

AF:

0.00327

Gnomad NFE exome

AF:

0.00375

Gnomad OTH exome

AF:

0.00314

GnomAD4 exome

AF:

0.000703

AC:

852

AN:

1211410

Hom.:

AF XY:

0.000812

AC XY:

482

AN XY:

593408

show subpopulations

Gnomad4 AFR exome

AF:

0.000737

Gnomad4 AMR exome

AF:

0.00200

Gnomad4 ASJ exome

AF:

0.00143

Gnomad4 EAS exome

AF:

0.000309

Gnomad4 SAS exome

AF:

0.00340

Gnomad4 FIN exome

AF:

0.00183

Gnomad4 NFE exome

AF:

0.000477

Gnomad4 OTH exome

AF:

0.000942

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000666

AC:

AN:

150188

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73310

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000661

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

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

IFNGR2-related disorder

Benign:1

Jul 15, 2024

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over