22-37226705-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_002872.5(RAC2):c.547C>T(p.Arg183Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00000186 in 1,612,928 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R183Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_002872.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RAC2 | NM_002872.5 | c.547C>T | p.Arg183Trp | missense_variant | 6/7 | ENST00000249071.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RAC2 | ENST00000249071.11 | c.547C>T | p.Arg183Trp | missense_variant | 6/7 | 1 | NM_002872.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152042Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000400 AC: 1AN: 249862Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135402
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1460886Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726774
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152042Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74258
ClinVar
Submissions by phenotype
Neutrophil immunodeficiency syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 08, 2022 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt RAC2 protein function. ClinVar contains an entry for this variant (Variation ID: 432838). This variant has not been reported in the literature in individuals affected with RAC2-related conditions. This variant is present in population databases (rs138762569, gnomAD 0.007%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 183 of the RAC2 protein (p.Arg183Trp). - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 21, 2017 | The R183W variant in the RAC2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R183W variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In addition, this substitution occurs at a position where amino acids with similar properties to Arginine are tolerated across species. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret R183W as a variant of uncertain significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at