Table 1.
Synonymous variants identified in MDS patients.
| Patient no. (ID) | GATA2 mutation | Genomic DNA VAF% (total depth) | cDNA VAF% WT/Mut (total depth) | Evol conser/ PhysChem diff | CADD/GAVIN (C2; P > 26, B < 19) | gnomAD browser MAF% (mutant/total) | Splicing prediction |
|---|---|---|---|---|---|---|---|
| P1 (D 1239) | c.351C>G; p.T117T | WES50% (160), DS47% (766) | DS99.88%/0.006% (320215) | Medium/none | 10.5/B | None | Cryptic donor, new ESS site |
| P2 (sister of P1) | c.351C>G; p.T117T | Heterozygous (Sanger) | Not done | As above | As above | As above | As above |
| P3 (D 749) | c.351C>G; p.T117T | WES47% (130), DS51% (703) | DS99.89%/0.004% (838094) | As above | As above | As above | As above |
| P4 (LT) | c.649C>T; p.L217L | WES48% (196), DS51% (725) | DS79.43%/20.56% (429616) | High/none | 10.7/B | 0.001% (2/246096) | None |
| P5 (D 722) | c.981G>A; p.G327G | WES52% (156), DS48% (788) | DS99.96%/0.014% (7190) | Medium/none | 18.5/B | None | New ESS site |
| P6 (D 1142) | c.1023C>T; p.A341A | WES47% (296), DS49% (1449) | DS99.91%/0.095% (4213) | Weak/none | 15.4/B | 0.002% (6/275438) | ESE site broken |
| P7 (D) | c.1416G>A; p.P472P | WES49% (63) | DS99.91%/0.085% (388784) | Medium/none | 12.4/B | 0.027% (70/256322) | None |
| P8 (I 386) | c.1416G>A; p.P472P | Heterozygous (Sanger) | Not done | As above | As above | As above | As above |
| P9 (UKA2604) | c.351C>G; p.T117T | Heterozygous (Sanger) | Not done | Medium/none | 10.5/B | None | Cryptic donor, new ESS site |
Gene annotation: GATA2 (NM_032638.4).
VAF variant allelic frequency, WT wild-type allele, Mut mutated allele, WES whole exome sequencing, DS deep sequencing, Sanger identified by Sanger sequencing, Evol (evolutionary) conservation assessed using Phylop and PhastCons, PhysChem diff physicochemical difference between amino acids, CADD combined annotation-dependent depletion score, GAVIN Gene-Aware Variant Interpretation (C2: CADD scores significantly predictive for pathogenicity (p < 0.05), P pathogenic if CADD > 26, B benign if CADD lower than 19), MAF minor allelic frequency, Splicing prediction Human Splicing Finder v. 3.0. ESS exonic splicing silencer, ESE exonic splicing enhancer.