Analysis of clinical and genomic profiles of therapy-related myeloid neoplasm in Korea

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 NM_032043.3	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 NM_000267.3	Neurofibromatosis (AD)	c.1595T>G	p.Leu532Arg	0.68/81	P (★)/DM (high)	0/0	LP (PM1 + PM2 + PP3 + PP5)
tmn30^†	M/54	CEBPA NM_004364.4	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 NM_020937.4	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 NM_016222.4	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 NM_001754.4	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 NM_002485.4	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

ISSN: 1479-7364