chr21-33403562-T-TGGTCGCTGCTGC
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_005534.4(IFNGR2):c.20_31dup(p.Leu10_Leu11insArgSerLeuLeu) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000294 in 1,360,550 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000047 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000027 ( 0 hom. )
Consequence
IFNGR2
NM_005534.4 inframe_insertion
NM_005534.4 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.240
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 Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
IFNGR2 | NM_005534.4 | c.20_31dup | p.Leu10_Leu11insArgSerLeuLeu | inframe_insertion | 1/7 | ENST00000290219.11 | NP_005525.2 | |
IFNGR2 | NM_001329128.2 | c.20_31dup | p.Leu10_Leu11insArgSerLeuLeu | inframe_insertion | 1/8 | NP_001316057.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
IFNGR2 | ENST00000290219.11 | c.20_31dup | p.Leu10_Leu11insArgSerLeuLeu | inframe_insertion | 1/7 | 1 | NM_005534.4 | ENSP00000290219 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000466 AC: 7AN: 150308Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.0000273 AC: 33AN: 1210132Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 16AN XY: 593904
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GnomAD4 genome AF: 0.0000465 AC: 7AN: 150418Hom.: 0 Cov.: 32 AF XY: 0.0000272 AC XY: 2AN XY: 73506
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Immunodeficiency 28 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 26, 2021 | This variant, c.20_31dup, results in the insertion of 4 amino acid(s) to the IFNGR2 protein (p.Leu10_Leu11insArgSerLeuLeu), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has not been reported in the literature in individuals affected with IFNGR2-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at