Table 2.
C3 glomerulopathy – Genetic Analysis
| C3G | Age/Sex | Gene | Variant | Highest MAFa | Populationb | PPc | CADDd | Interpretatione | |
|---|---|---|---|---|---|---|---|---|---|
| 1 | C3GN | 64/F | CFH | c.349G>A, p.Gly117Arg | No data | No data | 4/5 | 31 | Likely pathogenic |
| c.497G>A, p.Arg166Gln | 0.05% | NFE | 1/5 | 0.36 | VUS | ||||
| 2 | C3GN | 27/F | C3 | c.2390A>T, p.Asp797Val | No data | No data | 6/6 | 31 | Likely pathogenic |
| 3 | C3GN | 29/M | C8G | c.276–3C>T | 0.52% | AFR | N/A | N/A | VUS |
| 4 | C3GN | 42/F | CFI | c.782G>A, p.Gly261Asp | 0.20% | NFE | 1/6 | 8.26 | VUS |
| 5 | C3GN | 53/F | CFHR5 | c.646–647delinsTT, p.Asn216Phe | 0.01% | NFE | N/A | N/A | Pathogenic |
| 6 | C3GN | 73/F | CFH | c.2171delC, p.Thr724fs*725 | No data | No data | N/A | N/A | Pathogenic |
| 7 | C3GN | 47/F | C3 | c.2390A>T, p.Asp797Val | No data | No data | 6/6 | 31 | Likely pathogenic |
| 8 | C3GN | 23/M | CFH | c.3350A>G, p.Asn1117Ser | No data | No data | 22.8 | VUS | |
| 9 | C3GN | 69/M | CFH | c.2557T>C p.Cys853Arg | No data | No data | 5/5 | 24.1 | Pathogenic |
| 10 | C3GN | 4/M | CFH | c.497G>A, p.Arg166Gln | 0.05% | NFE | 1/5 | 0.36 | VUS |
| 11 | C3GN | 21/M | C8A | c.465G>T, p.Gly155Gly | No data | No data | N/A | N/A | VUS |
| 12f | C3GN | 20/M | C3 | c.463A>C p.Lys155GIn | 0.059% | NFE | 1/6 | 5.73 | VUS |
| 13 | C3GN | 15/F | CFHR2 | c.212C>T, p.Thr71Met | No data | No data | 0/6 | 18.04 | VUS |
| 14 | C3GN | 12/F | C5 | c.734A>G, p.Asn245Ser | 0.42% | EAS | 2/6 | 12.76 | VUS |
| 15 | C3GN | 19/M | C3 | c.2488T>G, p.Phe830Val | No data | No data | 6/6 | 25.2 | VUS |
| C8B | c.1144G>T, p.Asp382Tyr | 0.62% | NFE | 4/6 | 28.2 | VUS | |||
| 16 | C3GN | 34/F | C3 | c.2770G>A, p.Gly924Ser | No data | No data | 5/6 | 31 | VUS |
| 17 | C3GN | 42/F | C3 | c.463A>C, p.Lys155Gln | 0.59% | NFE | 1/6 | 5.73 | VUS |
| 18 | C3GN | 45/F | CFH | c.739delG, p.Gly247Glufs*34 | No data | No data | N/A | N/A | Pathogenic |
| 19 | C3GN | 28/M | CFHR5 | c.254–5C>T | 0.65% | FIN | N/A | N/A | VUS |
| 20 | C3GN | 22/M | C5 | c.3706G>C, p.Asp1236His | 0.01% | NFE | 5/6 | 23.9 | VUS |
| C8B | C.1625C>T, p.Thr542Ile | 0.76% | NFE | 1/6 | 0.033 | VUS | |||
| CFH | c.2867C>T, p.Thr956Met | 0.30% | SAS | 2/5 | 15.09 | VUS | |||
| 21 | C3GN | 14/M | C9 | c.499C>T, p.Pro167Ser | 0.66% | NFE | 5/6 | 25.3 | VUS |
| 22f | C3GN | 50/M | CFHR5 | c.254–5C>T | 0.65% | FIN | N/A | N/A | VUS |
| 23 | C3GN | 43/M | CFHR5 | c.1343A>T,p.Tyr448Phe | No data | No data | 2/5 | 12.72 | VUS |
| 24 | C3GN | 55/M | CFH | c.705T>A, p.Tyr235Stop | No data | No data | 2/4 | 35 | Pathogenic |
| CFI | c.1657C>T, p.Pro553Ser | 0.21% | NFE | 2/6 | 15.35 | VUS | |||
| 25 | DDD | 22/M | CFH | c.2850G>T, p.Gln950His | 0.66% | NFE | 2/5 | 21.4 | VUS |
| 26 | DDD | 51/F | CFH | c.3628C>T, p.Arg1210Cys | 0.03% | NFE | 1/5 | 11.77 | Pathogenic |
Abbreviations:
MAF minor allele frequency
Populations= NFE: Non-Finnish European; SAS: South Asian; AFR: African/African American; EAS: East Asian; FIN: Finnish
PP= Pathogenicity prediction: Pathogenicity prediction score using a maximum of 6 computational methods (PhyloP, SIFT, LRT, Mutation Taster, PolyPhen HDIV, and GERP) to assess functional significance and conservation of missense variants. A score of ≥4 (out of 4, 5, or 6) is generally considered to indicate a variant is more likely to be pathogenic than benign, but pathogenicity predictions are used only as a guideline to aid interpretation and are not used solely to determine pathogenicity.
CADD= Combined Annotation Dependent Depletion: http:wintervar.wglab.org; indication of the deleteriousness of a genetic variant
Interpretation= Variants are interpreted as VUS (variant of uncertain significance), likely pathogenic, pathogenic based on criteria developed by the American College of Medical Genetics and Genomics
Patient 12 and 22 had a positive MIg