ClinVar Miner

Submissions for variant NM_001303256.3(MORC2):c.848G>A (p.Arg283His)

gnomAD frequency: 0.00002  dbSNP: rs1482880426
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001223836 SCV001396002 uncertain significance Charcot-Marie-Tooth disease axonal type 2Z 2023-04-11 criteria provided, single submitter clinical testing 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 expected to disrupt MORC2 protein function. ClinVar contains an entry for this variant (Variation ID: 951841). This missense change has been observed in individual(s) with Charcot-Marie-Tooth disease, type 2 (PMID: 26659848). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 283 of the MORC2 protein (p.Arg283His).
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV003737028 SCV004563784 uncertain significance not provided 2023-09-26 criteria provided, single submitter clinical testing The MORC2 c.848G>A; p.Arg283His variant (rs1482880426) is reported in the literature in a family affected with Charcot–Marie–Tooth disease type 2, but failed to segregate with disease (Albulym 2016). This variant is also reported in ClinVar (Variation ID: 951841) and is only observed on one allele in the Genome Aggregation Database, indicating it is not a common polymorphism. Computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.34). Due to limited information, the clinical significance of this variant is uncertain at this time. References: Albulym OM et al. MORC2 mutations cause axonal Charcot-Marie-Tooth disease with pyramidal signs. Ann Neurol. 2016 Mar;79(3):419-27. PMID: 26659848.

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