chr21-33403551-C-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_005534.4(IFNGR2):āc.8C>Gā(p.Pro3Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000752 in 1,329,646 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Synonymous variant affecting the same amino acid position (i.e. P3P) has been classified as Likely benign.
Frequency
Consequence
NM_005534.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IFNGR2 | NM_005534.4 | c.8C>G | p.Pro3Arg | missense_variant | 1/7 | ENST00000290219.11 | |
IFNGR2 | NM_001329128.2 | c.8C>G | p.Pro3Arg | missense_variant | 1/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IFNGR2 | ENST00000290219.11 | c.8C>G | p.Pro3Arg | missense_variant | 1/7 | 1 | NM_005534.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000664 AC: 1AN: 150626Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000678 AC: 4AN: 58956Hom.: 0 AF XY: 0.000114 AC XY: 4AN XY: 35084
GnomAD4 exome AF: 0.00000763 AC: 9AN: 1179020Hom.: 0 Cov.: 30 AF XY: 0.0000121 AC XY: 7AN XY: 576986
GnomAD4 genome AF: 0.00000664 AC: 1AN: 150626Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 73508
ClinVar
Submissions by phenotype
Immunodeficiency 28 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 26, 2022 | This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 3 of the IFNGR2 protein (p.Pro3Arg). This variant is present in population databases (rs773084508, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with IFNGR2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1496111). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at