rs141609920
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_005534.4(IFNGR2):c.249G>A(p.Gly83=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000372 in 1,613,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000036 ( 0 hom. )
Consequence
IFNGR2
NM_005534.4 synonymous
NM_005534.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.312
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
Variant 21-33421522-G-A is Benign according to our data. Variant chr21-33421522-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 474967.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.312 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IFNGR2 | NM_005534.4 | c.249G>A | p.Gly83= | synonymous_variant | 3/7 | ENST00000290219.11 | |
IFNGR2 | NM_001329128.2 | c.306G>A | p.Gly102= | synonymous_variant | 4/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IFNGR2 | ENST00000290219.11 | c.249G>A | p.Gly83= | synonymous_variant | 3/7 | 1 | NM_005534.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152038Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
7
AN:
152038
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000437 AC: 11AN: 251448Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135890
GnomAD3 exomes
AF:
AC:
11
AN:
251448
Hom.:
AF XY:
AC XY:
5
AN XY:
135890
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000363 AC: 53AN: 1461824Hom.: 0 Cov.: 33 AF XY: 0.0000303 AC XY: 22AN XY: 727216
GnomAD4 exome
AF:
AC:
53
AN:
1461824
Hom.:
Cov.:
33
AF XY:
AC XY:
22
AN XY:
727216
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152038Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74258
GnomAD4 genome
?
AF:
AC:
7
AN:
152038
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74258
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Immunodeficiency 28 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 01, 2021 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Sep 01, 2022 | IFNGR2: BP4, BP7 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at