Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory of Medical Genetics, |
RCV001822991 | SCV002072487 | pathogenic | SYNGAP1-related encephalopathy | 2022-01-30 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001869805 | SCV002285442 | likely pathogenic | Intellectual disability, autosomal dominant 5 | 2021-07-14 | criteria provided, single submitter | clinical testing | |
| Victorian Clinical Genetics Services, |
RCV001869805 | SCV002766726 | likely pathogenic | Intellectual disability, autosomal dominant 5 | 2021-05-06 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as likely pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with SYNGAP1-related intellectual disability. While loss of function is established for protein truncating variants, it is also a likely mechanism of disease for missense variants although a dominant-negative mechanism of disease cannot be excluded (PMIDs: 23161826, 26079862). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0211 - Canonical splice site variant without proven consequence on splicing (no functional evidence available). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0505 - Abnormal splicing is predicted by in silico tools and affected nucleotide is highly conserved. (SP) 0703 - Other splice variants comparable to the one identified in this case have moderate previous evidence for pathogenicity. A de novo c. 1676 + 2T>C canonical splice site variant was identified in an individual with intellectual disability and a de novo c.1676+5 G>A splice region variant was identified in an individual with severe intellectual disability, epilepsy and autistic features. RT-PCR of patient cDNA carrying the latter demonstrated activation of a crytic donor site 37bp upstream of the WT donor site, resulting in a frameshift and premature stop codon (PMIDs: 28333917, 28576131). (SP) 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) 1102 - Strong phenotype match for this individual. (SP) 1204 - This variant has been shown to be de novo in the proband (parental status not tested but assumed) (by trio analysis). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
| Laboratory of Medical Genetics, |
RCV001869805 | SCV004014000 | pathogenic | Intellectual disability, autosomal dominant 5 | 2021-12-09 | criteria provided, single submitter | clinical testing | PVS1, PS2, PM2, PP3 |