Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP2BP4_StrongBP6_Very_StrongBS2
The NM_015271.5(TRIM2):c.122G>A(p.Arg41His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00182 in 1,613,988 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R41C) has been classified as Uncertain significance.
TRIM2 (HGNC:15974): (tripartite motif containing 2) The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The protein localizes to cytoplasmic filaments. It plays a neuroprotective role and functions as an E3-ubiquitin ligase in proteasome-mediated degradation of target proteins. Mutations in this gene can cause early-onset axonal neuropathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), TRIM2. . Gene score misZ 3.5715 (greater than the threshold 3.09). Trascript score misZ 3.9409 (greater than threshold 3.09). GenCC has associacion of gene with Charcot-Marie-Tooth disease type 2R.
BP4
Computational evidence support a benign effect (MetaRNN=0.020416021).
BP6
Variant 4-153270426-G-A is Benign according to our data. Variant chr4-153270426-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 474610.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-153270426-G-A is described in Lovd as [Likely_benign].
Likely benign, criteria provided, single submitter
clinical testing
GeneDx
Aug 05, 2020
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Likely benign, criteria provided, single submitter
clinical testing
CeGaT Center for Human Genetics Tuebingen
May 01, 2024
ENSG00000288637: BS2; TRIM2: BS2 -
Charcot-Marie-Tooth disease type 2R Benign:2
Likely benign, criteria provided, single submitter
clinical testing
Invitae
Jan 31, 2024
- -
Likely benign, criteria provided, single submitter
clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Oct 30, 2019
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TRIM2-related disorder Benign:1
Likely benign, criteria provided, single submitter
clinical testing
PreventionGenetics, part of Exact Sciences
Oct 04, 2022
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -