Table 2.
Deleterious presumed/potential germline variants identified among 53 T-MN patients
| Patient ID | Sex/age | Gene and RefSeq | Syndrome (inheritance) | Coding DNA sequence | Amino acid change | VAF/total depth | ClinVar‡/HGMD§ | gnomAD exomes frequency (global/ea-st asians) | ACMG classif-ication |
|---|---|---|---|---|---|---|---|---|---|
| tmn01 | M/67 |
BRIP1 |
Fanconi anemia (AR) | c.1794+1G>A | – | 0.55/164 | LP (★★)/not reported | 0.00000796/0.000109 | P (PVS1 + PM2 + PP5) |
| tmn12† | M/53 |
NF1 |
Neurofibromatosis (AD) | c.1595T>G | p.Leu532Arg | 0.68/81 | P (★)/DM (high) | 0/0 | LP (PM1 + PM2 + PP3 + PP5) |
| tmn30† | M/54 |
CEBPA |
Familia AML (AD) | c.801_802delCG | p.Gly268fs (not anticipated to occur NMD) | 0.35/17 | None/none | 0/0 | LP (PVS1_Strong + PM2) |
| tmn36* | F/53 |
FANCM |
Fanconi anemia (AR) | c.1972C>T | p.Arg658* (NMD) | 0.44/296 | Conflicting interpretations of pathogenicity (★)/DM (high) | 0.0000757/0 | P (PVS1 + PM2 + PP5) |
| tmn40* | F/62 |
DDX41 |
Familial myeloproliferative/lymphoproliferative neoplasms (AD) | c.308_309delAG | p.Glu103fs (NMD) | 0.50/111 | None/none | 0/0 | LP (PVS1 + PM2) |
| tmn49* | M/17 |
RUNX1 |
Familial platelet disorder with propensity to myeloid malignancy | c.39C>G | p.Tyr13* (NMD) | 0.46/426 | None/none | 0/0 | LP (PVS1 + PM2) |
| tmn52* | M/17 |
NBN |
Nijmegen breakage syndrome (AR) | c.2206G>T | p.Glu736* (not anticipated to occur NMD) | 0.54/162 | US (★★)/DM? (low) | 0.000004/0.0000544 | LP (PVS1_Strong + PM2) |
RefSeq Reference sequence; AD Autosomal dominant; AR Autosomal recessive; NMD Nonsense mediated decay; VAF Variant allele frequency; HGMD The human gene variant database; gnomAD The genome aggregation database; ACMG American College of Medical Genetics and Genomics; P Pathogenic; LP Likely pathogenic; US Uncertain significance; DM Disease causing variant; DM? Likely disease causing variant; VUS Variants of uncertain significance; PVS Pathogenic very strong; PM Pathogenic moderate; PP Pathogenic supporting
*Presumed germline variants via non-malignant BM samples
†Classified as both germline and somatic variants since these variants can be both
‡ClinVar reports were described with clinical significance and review status. The number of stars (★) refers to the review status of ClinVar: criteria provided, conflicting interpretations (★); criteria provided, multiple submitters, no conflicts (★★)
§HGMD reports were described with variant class and confidence