In silico prediction of GoF activity in JAK1 variants
| Variant class . | JAK1 variant . | Predicted deleterious (Y/N) . | Frequency, BioME (v1.2) . | ||
|---|---|---|---|---|---|
| Transcript | Protein | (CADD) (Rentzsch et al., 2019, Kircher et al., 2014) | (Sevim Bayrak et al., 2021) | n = 30,814 | |
| Exceedingly rare Severe GoF | c.1901C>A c.2108G>T | p.Ala634Asp p.Ser703Ile | Y (32) Y (26.1) | Y (GoF) Y (GoF) | Private, n = 0 Private, n = 0 |
| Ultra-rare or rare Mild-to-moderate GoF | c.415C>T c.1516C>T c.2099G>A c.2953G>A | p.Glu139Lys p.Arg506Cys p.Ser700Asn p.Val985Ile | Y (22.6) Y (21.2) Y (25.1) Y (18.2) | Y (GoF) Y (GoF) Y (GoF) N (neutral) | Private, n = 0 5.63 × 10−04, n = 31 1.66 × 10−05, n = 1 1.82 × 10−04, n = 11 |
| Total = 43 (0.14%) | |||||
| Ultra-rare or rare Predicted GoF | c.287C>T c.296A>G c.379T>A c.779G>C c.1078C>T c.1439C>T c.1889A>G c.1951G>A c.2005T>G c.2111A>G c.2414T>A c.2498A>G c.2617C>T c.2675G>A c.3230A>G | p.Thr96Ile p.Asp99Gly p.Trp127Arg p.Ser260Thr p.Arg360Trp p.Thr480Ile p.Asp630Gly p.Val651Met p.Phe669Val p.Tyr704Cys p.Phe805Tyr p.Asn833Ser p.Arg873Cys p.Cys892Tyr p.Tyr1077Cys | Y (21.7) Y (23.3) Y (25.4) Y (20.4) Y (25.1) Y (22.5) Y (33.0) Y (27.6) Y (28.2) Y (27.2) Y (29.7) Y (15.8) Y (32.0) Y (24.8) Y (31.0) | Y (GoF) Y (GoF) Y (GoF) Y (GoF) Y (GoF) Y (GoF) Y (GoF) Y (GoF) Y (GoF) Y (GoF) Y (GoF) Y (GoF) Y (GoF) Y (GoF) Y (GoF) | 1.66 × 10−05, n = 1 1.66 × 10−05, n = 1 1.66 × 10−05, n = 1 1.66 × 10−05, n = 1 4.97 × 10−05, n = 3 1.66 × 10−05, n = 1 1.66 × 10−05, n = 1 9.77 × 10−04, n = 59 1.66 × 10−05, n = 1 1.66 × 10−05, n = 1 1.66 × 10−05, n = 1 1.36 × 10−03, n = 80 1.66 × 10−05, n = 1 1.66 × 10−05, n = 1 4.97 × 10−05, n = 3 |
| Total = 156 (0.51%) | |||||
| Variant class . | JAK1 variant . | Predicted deleterious (Y/N) . | Frequency, BioME (v1.2) . | ||
|---|---|---|---|---|---|
| Transcript | Protein | (CADD) (Rentzsch et al., 2019, Kircher et al., 2014) | (Sevim Bayrak et al., 2021) | n = 30,814 | |
| Exceedingly rare Severe GoF | c.1901C>A c.2108G>T | p.Ala634Asp p.Ser703Ile | Y (32) Y (26.1) | Y (GoF) Y (GoF) | Private, n = 0 Private, n = 0 |
| Ultra-rare or rare Mild-to-moderate GoF | c.415C>T c.1516C>T c.2099G>A c.2953G>A | p.Glu139Lys p.Arg506Cys p.Ser700Asn p.Val985Ile | Y (22.6) Y (21.2) Y (25.1) Y (18.2) | Y (GoF) Y (GoF) Y (GoF) N (neutral) | Private, n = 0 5.63 × 10−04, n = 31 1.66 × 10−05, n = 1 1.82 × 10−04, n = 11 |
| Total = 43 (0.14%) | |||||
| Ultra-rare or rare Predicted GoF | c.287C>T c.296A>G c.379T>A c.779G>C c.1078C>T c.1439C>T c.1889A>G c.1951G>A c.2005T>G c.2111A>G c.2414T>A c.2498A>G c.2617C>T c.2675G>A c.3230A>G | p.Thr96Ile p.Asp99Gly p.Trp127Arg p.Ser260Thr p.Arg360Trp p.Thr480Ile p.Asp630Gly p.Val651Met p.Phe669Val p.Tyr704Cys p.Phe805Tyr p.Asn833Ser p.Arg873Cys p.Cys892Tyr p.Tyr1077Cys | Y (21.7) Y (23.3) Y (25.4) Y (20.4) Y (25.1) Y (22.5) Y (33.0) Y (27.6) Y (28.2) Y (27.2) Y (29.7) Y (15.8) Y (32.0) Y (24.8) Y (31.0) | Y (GoF) Y (GoF) Y (GoF) Y (GoF) Y (GoF) Y (GoF) Y (GoF) Y (GoF) Y (GoF) Y (GoF) Y (GoF) Y (GoF) Y (GoF) Y (GoF) Y (GoF) | 1.66 × 10−05, n = 1 1.66 × 10−05, n = 1 1.66 × 10−05, n = 1 1.66 × 10−05, n = 1 4.97 × 10−05, n = 3 1.66 × 10−05, n = 1 1.66 × 10−05, n = 1 9.77 × 10−04, n = 59 1.66 × 10−05, n = 1 1.66 × 10−05, n = 1 1.66 × 10−05, n = 1 1.36 × 10−03, n = 80 1.66 × 10−05, n = 1 1.66 × 10−05, n = 1 4.97 × 10−05, n = 3 |
| Total = 156 (0.51%) | |||||