Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV000006526 | SCV005087202 | pathogenic | Focal segmental glomerulosclerosis 2 | 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: 0101 - Gain of function is a known mechanism of disease in this gene and is associated with glomerulosclerosis, focal segmental, 2 (MIM#603965). Missense variants have been functionally proven to result in increased calcium channel activity (PMID: 15879175, PMID: 32509715). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from proline to glutamine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0600 - Variant is located in the annotated ankyrin repeat domain (DECIPHER). (I) 0703 - Other missense variants comparable to the one identified in this case have moderate previous evidence for pathogenicity. One alternative change (p.(Pro112Arg)) was observed as de novo in an individual with sub-nephrotic range proteinuria (PMID: 32509715), and another alternative change (p.(Pro112Leu)) has been reported in an individual with focal segmental glomerulosclerosis (FSGS) and proteinuria, who also had a non-pathogenic variant in the COL4A5 gene (PMID: 31576025). (SP) 0803 - This variant has limited previous evidence of pathogenicity in an unrelated individual. This variant has been reported in a single family with FSGS (PMID: 15879175). (SP) 0901 - This variant has strong evidence for segregation with disease. This variant segregated in 20 affected individuals within a single family with FSGS (PMID: 15879175). (SP) 1002 - This variant has moderate functional evidence supporting abnormal protein function. Transfected cells showed increased intracellular calcium, increased angiotensin signalling and protein mislocalization (PMID: 15879175). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
| OMIM | RCV000006526 | SCV000026709 | pathogenic | Focal segmental glomerulosclerosis 2 | 2005-06-17 | no assertion criteria provided | literature only |