Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002018745 | SCV002261316 | uncertain significance | Charcot-Marie-Tooth disease axonal type 2Z | 2021-12-09 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 427 of the MORC2 protein (p.Lys427Arg). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MORC2-related conditions. 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. 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. |
| Laboratory of Functional Genomics, |
RCV005053990 | SCV005626397 | likely pathogenic | Developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy | criteria provided, single submitter | clinical testing | Variant c.1280A>G in MORC2 was found in a patient with clinical signs of DIFGAN syndrome. Segregation analysis confirmed its de novo origin. The c.1280A>G variant wasn't found in population databases. For functional characterization of the variant a vector, expressing MORC2 fused with Flag tag at C-terminal end, was created. Transfection of the plasmid into HEK293T cells followed by Western blotting revealed slight reduction of MORC2 protein quantity compared to wt vector. In summary, c.1280A>G variant meets criteria to be classified as likely pathogenic. |