21-33403544-A-G
Variant summary
Our verdict is Pathogenic. Variant got 13 ACMG points: 13P and 0B. PVS1PS1_ModeratePM2PP5
The NM_005534.4(IFNGR2):c.1A>G(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000607 in 1,318,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000051 ( 0 hom. )
Consequence
IFNGR2
NM_005534.4 start_lost
NM_005534.4 start_lost
Scores
4
2
10
Clinical Significance
Conservation
PhyloP100: 0.539
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]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 13 ACMG points.
PVS1
?
Start lost variant, no new inframe start found.
PS1
?
Another start lost variant in NM_005534.4 (IFNGR2) was described as [Likely_pathogenic] in ClinVar as 1066015
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 21-33403544-A-G is Pathogenic according to our data. Variant chr21-33403544-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 987732.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IFNGR2 | NM_005534.4 | c.1A>G | p.Met1? | start_lost | 1/7 | ENST00000290219.11 | |
IFNGR2 | NM_001329128.2 | c.1A>G | p.Met1? | start_lost | 1/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IFNGR2 | ENST00000290219.11 | c.1A>G | p.Met1? | start_lost | 1/7 | 1 | NM_005534.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000133 AC: 2AN: 150378Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000513 AC: 6AN: 1168492Hom.: 0 Cov.: 31 AF XY: 0.00000525 AC XY: 3AN XY: 571522
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GnomAD4 genome ? AF: 0.0000133 AC: 2AN: 150378Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 73374
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Immunodeficiency 28 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 08, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
P;P
Vest4
MutPred
Loss of disorder (P = 0.138);Loss of disorder (P = 0.138);
MVP
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at