Table 1.
Quick-reference for variant classification based on ACMG criteria
| IGD variant | ACMG criteria met | ACMG classification |
|---|---|---|
| A51T | BS1, BS3, BS4, BP4, BP5 | Benign |
| R85C | PM1, PP3, BS3, BS4, BP5 | Benign |
| D112Y | PM2, PP3, BS3, BS4 | Benign |
| S202G | BS3, BS4, BP4, BP5 | Benign |
| V331M | BS1, BS3, BS4, BP4, BP5 | Benign |
| M64V | PM2, BS3, BP4 | Likely Benign |
| V317L | PM2, BS3, BP4, BP5 | Likely Benign |
| R357W | BS3, BP4 | Likely Benign |
| S188L | PS3 (hom), BS3 (het), BS4, BP4 | Het Benign, Hom Uncertain Significance |
| V297I | PS3 (hom), BS 3 (het), BS4, BP4, BP5 | Het Benign, Hom Uncertain Significance |
| V158I | PS3 (hom), BS3 (het), BP4 | Het Likely Benign, Hom Uncertain Significance |
| R248Q | PS3 (hom), BS3 (het), BP4, BP5 | Het Likely Benign, Hom Uncertain Significance |
| R85L | PS3 (hom), BS3 (het) PM1, PP3, BP5 | Hom Likely Pathogenic, Het Likely Benign |
| Q210R | PS3 (hom), BS3 (het), PM2, PP3, BP2 | Hom Likely Pathogenic, Het Likely Benign |
| M323I | PS3 (hom), BS3 (het), PM2, PM3, BP4 | Hom Likely Pathogenic, Het Likely Benign |
| T260M | PS3 (hom), BS3 (het), PM3, PP3 | Hom Likely Pathogenic, Het Uncertain Significance |
| V274D | PS3 (hom), BS3 (het), PM2, PP3 | Hom Likely Pathogenic, Het Uncertain Significance |
| M111R | PS3, PM2, PM3, PP3, BP2 | Likely Pathogenic |
| Y113H | PS3, PM3, PP3 | Likely Pathogenic |
| R80C | PS3, PM2, PP3 | Likely Pathogenic |
| R85G | PS3, PM1, PP3 | Likely Pathogenic |
| R85H | PS3, PM1, PP3, BP5 | Likely Pathogenic |
| R164Q | PS3, PM2, PM3, PP3 | Likely Pathogenic |
| G234D | PS3, PM3, PP3 | Likely Pathogenic |
| W251L | PS3, PM2, PP3 | Likely Pathogenic |
| R270C | PS3, PM2, PP3 | Likely Pathogenic |
| N325K | PS3, PM2, PP3, BS4 | Likely Pathogenic |
| V115M | PS3, PP3 | Uncertain Significance |
| R117W | PS3, PP3 | Uncertain Significance |
| W178S | PS3, BP4 | Uncertain Significance |
| P290S | PS3, PP3, BS4 | Uncertain Significance |
| L173R | PS3, PS4, PP3, BS4, BP5 | Uncertain Significance |
| R268C | PS3, PM3, PP3, BS1, BP2, BP5 | Uncertain Significance |
| V334M | PS3 (hom), BS3 (het), PP3 | Uncertain Significance |
| KEY: | ||
|---|---|---|
| Term | Description | Evidence of impact |
| BS1 | Allele frequency greater than expected for disorder | Strong |
| BS3 | Well-established functional studies show no damaging effect | |
| BS4 | Lack of segregation in affected family members | |
| BP2 | In cis with a pathogenic variant in any inheritance pattern | Supporting |
| BP4 | Computational evidence suggesting no impact on gene or gene product | |
| BP5 | Found in a case with alternate molecular basis for disease | |
| Benign | 2 or more Strong | |
| Likely Benign | 1 Strong and 1 Supporting OR 2 or more Supporting | |
| PS3 | Well-established functional studies supportive of damaging effect | Strong |
| PS4 | Prevalence of variant in affected individuals significantly increased compared with controls | |
| PM1 | Located in a mutational hot spot and/or critical functional domain | Moderate |
| PM2 | Absent from controls (or extremely low frequency) | |
| PM3 | In trans with a pathogenic variant | |
| PP3 | Computational evidence supporting a deleterious effect | Supporting |
| Likely Pathogenic | 2 or more Strong OR 1 Strong and 1-2 Moderate OR 1 Strong 2 or more Supporting | |
| Uncertain Significance | Criteria not met OR contradictory criteria for Benign vs. Pathogenic | |
NOTE: Unused ACMG criteria (i.e. those not met by any variant) have been excluded from this table.