Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000991193 | SCV001134972 | likely pathogenic | not provided | 2019-10-14 | criteria provided, single submitter | clinical testing | The T24I variant in the MORC2 gene has been observed as a de novo variant in internal GeneDx whole exome sequencing data in association with developmental delay, hearing loss, short stature, microcephaly, muscle weakness, abnormal muscle tone, brain abnormalities, and dysmorphic features. The T24I variant is not observed in large population cohorts (Lek et al., 2016). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Therefore, we interpret T24I as a likely pathogenic variant. |
| Baylor Genetics | RCV003333113 | SCV004041173 | likely pathogenic | Charcot-Marie-Tooth disease axonal type 2Z | 2023-08-03 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV001281380 | SCV004041312 | likely pathogenic | Developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy | 2023-08-03 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001281380 | SCV005884055 | likely pathogenic | Developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy | 2024-12-11 | criteria provided, single submitter | clinical testing | Variant summary: MORC2 c.71C>T (p.Thr24Ile) results in a non-conservative amino acid change in the encoded protein sequence. Three of four in-silico tools predict a damaging effect of the variant on protein function. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 151518 control chromosomes. c.71C>T has been reported in the literature as de novo in an individual affected with Developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy (Guillen Sacoto_2020). At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in hyperactivation of Human Silencing Hub (HUSH)-mediated silencing (Guillen Sacoto_2020). The following publication has been ascertained in the context of this evaluation (PMID: 32693025). ClinVar contains an entry for this variant (Variation ID: 804228). Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| OMIM | RCV001281380 | SCV001468676 | pathogenic | Developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy | 2021-01-11 | no assertion criteria provided | literature only |