rs146252965
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_015271.5(TRIM2):c.497G>A(p.Arg166Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000595 in 1,613,196 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R166W) has been classified as Uncertain significance.
Frequency
Consequence
NM_015271.5 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 |
---|---|---|---|---|---|---|---|
TRIM2 | NM_015271.5 | c.497G>A | p.Arg166Gln | missense_variant | 4/12 | ENST00000338700.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRIM2 | ENST00000338700.10 | c.497G>A | p.Arg166Gln | missense_variant | 4/12 | 1 | NM_015271.5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152164Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000720 AC: 18AN: 250146Hom.: 0 AF XY: 0.0000665 AC XY: 9AN XY: 135250
GnomAD4 exome AF: 0.0000589 AC: 86AN: 1461032Hom.: 0 Cov.: 30 AF XY: 0.0000619 AC XY: 45AN XY: 726758
GnomAD4 genome ? AF: 0.0000657 AC: 10AN: 152164Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74342
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Dec 12, 2018 | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Charcot-Marie-Tooth disease type 2R Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 03, 2023 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 139 of the TRIM2 protein (p.Arg139Gln). This variant is present in population databases (rs146252965, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with TRIM2-related conditions. ClinVar contains an entry for this variant (Variation ID: 474609). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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