Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV002471555 | SCV002768306 | likely benign | X-linked intellectual disability with marfanoid habitus | 2022-02-02 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Likely benign. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with Lujan-Fryns syndrome (MIM#309520), Ohdo syndrome (MIM#300895), Opitz-Kaveggia syndrome (MIM#305450) and Hardikar syndrome (PMID: 33244166). (I) 0109 - This gene is associated with X-linked recessive disease. However, females with de novo variants resulting in a premature termination codon, have been reported with severe disease onset and heavily skewed X-inactivation. Carriers of missense variants have variable presentations, with some mildly affected and others asymptomatic (OMIM, PMIDs: 32174975, 30006928, 33244166). (I) 0115 - Variants in this gene are known to have variable expressivity which is commonly observed in affected females (PMIDs: 33244165; 33913598). (I) 0200 - Variant is predicted to result in a missense amino acid change from serine to proline. (I) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD (v2) <0.001 for a recessive condition (1 heterozygote, 0 homozygotes, 1 hemizygote). (SP) 0503 - Missense variant consistently predicted to be tolerated by multiple in silico tools or not conserved in placental mammals with a minor amino acid change. (SB) 0600 - Variant is located in the annotated eukaryotic mediator 12 subunit domain (DECIPHER). (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1206 - This variant has been shown to be paternally inherited (by trio analysis). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |