Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Undiagnosed Diseases Network, |
RCV003985512 | SCV002098350 | pathogenic | MED12-related disorder | 2024-07-03 | criteria provided, single submitter | clinical testing | |
| Genetics Laboratory, |
RCV002287504 | SCV002577676 | likely pathogenic | Blepharophimosis - intellectual disability syndrome, MKB type | 2022-10-04 | criteria provided, single submitter | clinical testing | PP5_strong;PM2_supporting;PM6;PP2;PP3 |
| 3billion | RCV003152766 | SCV003841805 | likely pathogenic | Cholestasis-pigmentary retinopathy-cleft palate syndrome | 2023-02-23 | criteria provided, single submitter | clinical testing | The variant is not observed in the gnomAD v2.1.1 dataset. Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.68; 3Cnet: 0.85). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with MED12 related disorder (ClinVar ID: VCV001210242 / PMID: 33244165). The variant has been previously reported as de novo in a similarly affected individual (PMID: 33244165). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline. |
| Victorian Clinical Genetics Services, |
RCV004594366 | SCV005086999 | pathogenic | MED12-related intellectual disability syndrome | 2023-07-17 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. 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 (MIM#301068). [MONDO contains a collective term (MED12-related intellectual disability syndrome (MONDO:0100000)]. (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) 0200 - Variant is predicted to result in a missense amino acid change from arginine to tryptophan. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0603 - Missense variant in a region that is highly intolerant to missense variation (high constraint region in DECIPHER). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been reported as likely pathogenic and as a VUS (LOVD, ClinVar), but also described as de novo in at least three females with a nonspecific neurodevelopmental disorder (PMID: 33244165, PMID: 34079076). (SP) 1203 - This variant has been shown to be de novo in the proband (parental status confirmed, by trio analysis). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
| Gene |
RCV001580311 | SCV001809987 | not provided | FG syndrome 1 | no assertion provided | literature only | De novo variant in 4 females with nonspecific intellectual disability |