Table 2. Overview of all P/LP confirmed... | American Society of Hematology

Table 2.

Overview of all P/LP confirmed germ line variants detected in this cohort of patients with MDS

ID	Shared	Gene	Inheri-tance	Variant type	cDNA	Protein	Transcript	VAF	ACMG/AMP classifi-cation	Age at diagnosis (y)	MDS WHO 2008 classification	Somatic driver variants	Outcome
1R∗	Yes	BARD1	AD	Frameshift	c.1935_1954dup	p.Glu652Valfs∗69	NM_000465.4	0.61	LP	64	RAEB-2	—	Alive
2R∗	Yes	BLM	AD	Frameshift	c.2506_2507del	p.Arg836Glyfs∗18	NM_000057.4	0.52	LP	71	CMML	MPL p.Ser204Pro TET2 p.Arg544Ter TET2 p.Gln1053Ter	Relapse, death from infection
3R∗	Yes	BLM	AD	Nonsense	c.1642C>T	p.Gln548∗	NM_000057.4	0.43	LP	57	MDS, unclassifiable†	—	Alive
4R∗	Yes	BRCA2	AD	Frameshift	c.5946delT	p.Ser1982Argfs∗22	NM_000059.4	0.51	P	52	RAEB-1†	RAD50 p.Asn934Lysfs TP53 p.Lys132Glu	Relapse, death from primary disease
5R∗	Yes	BRCA2	AD	Frameshift	c.5946delT	p.Ser1982Argfs∗22	NM_000059.4	0.58	P	59	RCMD†	—	Relapse, death from primary disease
6R∗	Yes	BRCA2	AD	Nonsense	c.5217_5223del	p.Tyr1739∗	NM_000059.4	0.61	P	56	RAEB-2	TP53 c.783-1G>A PPM1D p.Val465Aspfs SMC1A p.Lys752Argfs	Relapse, death from primary disease
7R∗	Yes	BRIP1	AD	Frameshift	c.1236delA	p.Val413Phefs∗10	NM_032043.3	0.53	LP	63	RAEB-2	—	Relapse, death from infection
8R∗	Yes	BRIP1	AD	Frameshift	c.3196delT	p.Ser1066Hisfs∗12	NM_032043.3	0.45	LP	64	MDS, unclassifiable†	CBL p.Cys404Tyr DNMT3A p.Arg882His NRAS p.Gly12Asp SETBP1 p.Asp868Asn ASXL1 p.Tyr591Ter	Relapse, death from primary disease
9R∗	Yes	BRIP1	AD	Frameshift	c.2392C>T	p.Arg798∗	NM_032043.3	0.69	LP	60	RAEB-2	NF1 c.3198-1G>T	Relapse, death from primary disease
10R∗	Yes	CHEK2	AD	Frameshift	c.1229del	p.Thr410Metfs∗15	NM_001005735.2	0.39	P	49	MDS, unclassifiable	—	Relapse, alive
11R∗	Yes	CHEK2	AD	Frameshift	c.1392delT	p.Ser465Valfs∗15	NM_001005735.2	0.53	LP	54	MDS associated with isolated del(5q)	NFE2 p.Arg323Alafs CSNK1A1 p.Asp140Ala	Alive
12R	No	DDX41	AD	Nonsense	c.415_418dup	p.Asp140Glyfs∗2	NM_016222.4	0.43	P	66	MDS, unclassifiable	ASXL1 p.Gly646Trpfs	Alive
13R	No	DDX41	AD	Nonsense	c.415_418dup	p.Asp140Glyfs∗2	NM_016222.4	0.49	P	57	RAEB-2	—	Alive
14R∗	Yes	DDX41	AD	Nonsense	c.415_418dup	p.Asp140Glyfs∗2	NM_016222.4	0.42	P	49	RAEB-2	—	Alive
15R	No	DDX41	AD	Frameshift	c.155dupA	p.Arg53Alafs∗16	NM_016222.4	0.49	P	69	RAEB-2	—	Relapse, death from primary disease
16R	Yes	ERCC6L2	AR	Nonsense	c.19C>T	p.Gln7∗	NM_001010895.4	1	LP	34	RAEB-1	SF3B1 p.Arg238Cys TP53 p.Arg175His	Relapse, death from primary disease
17R	Yes	FANCA	AR	Indel	c.3791_3793del	p.Ser1264del	NM_000135.4	1	P	11	RAEB-2	—	Nonrelapse mortality, cause of death not specified
18R	Yes	FANCG	AR	Frameshift	c.907_908dup	p.Glu304Trpfs∗4	NM_004629.2	0.93	LP	27	RA	ASXL1 p.Arg693Ter	Alive
19R∗	Yes	MRE11	AD	Nonsense	c.1516G>T	p.Glu506∗	NM_005591.4	0.54	LP	54	RCMD†	—	Death from infection
20R∗	Yes	MSH6	AD	Frameshift	c.1634_1635del	p.Lys545Argfs∗17	NM_000179.3	0.46	P	49	RA†	—	Nonrelapse mortality, death from secondary malignancy
21R∗	Yes	NBN	AD	Splicing	c.2071-1G>A	na	NM_002485.5	0.62	P	55	CMML	TET2 p.His667Ilefs GATA2 p.Met388_Lys389del RUNX1 p.Leu161_Arg162insSer CBL p.Leu380Pro SRSF2 p.Pro95Leu TET2 p.Lys875Ter	Primary graft failure/rejection, alive
22R∗	Yes	PALB2	AD	Copy number variant	na‡	na	NC_000016.10	0.52	LP	65	RAEB-2	—	Relapse, death from primary disease
23R∗	Yes	PMS2	AD	Nonsense	c.11C>G	p.Ser4∗	NM_001322015.2	0.41	LP	60	RCMD	—	Nonrelapse mortality, death from GVHD
24R	Yes/no§	SBDS	AR	Nonsense/splicing	c.184A>T/c.258+2T>C	p.Lys62∗/na	NM_016038.4	0.38/0.43	P/P	18	RAEB-2	—	Relapse, death from primary disease
25R	Yes/no§	SBDS	AR	Splicing/splicing	c.258+1G>C/c.258+2T>C	na/na	NM_016038.4	0.7/0.26	P/P	19	MDS associated with isolated del(5q)	TP53 c.559+1G>A	Alive
26R∗	Yes	TERT	AD	Nonsense	c.951G>A	p.Trp317∗	NM_198253.3	0.43	LP	51	RAEB-2	—	Alive
27R∗	Yes	TERT	AD	Nonsynonymous	c.193C>G	p.Pro65Ala	NM_198253.3	0.63	LP	64	RAEB-2	TP53 p.Arg248Gln TP53 p.Thr125Thr	Relapse, death from primary disease
28R∗	Yes	TNFRSF13B	AD	Frameshift	c.204dupA	p.Leu69Thrfs∗12	NM_012452.3	0.46	P	66	MDS, unclassifiable	—	Relapse, alive

ID	Shared	Gene	Inheri-tance	Variant type	cDNA	Protein	Transcript	VAF	ACMG/AMP classifi-cation	Age at diagnosis (y)	MDS WHO 2008 classification	Somatic driver variants	Outcome
1R∗	Yes	BARD1	AD	Frameshift	c.1935_1954dup	p.Glu652Valfs∗69	NM_000465.4	0.61	LP	64	RAEB-2	—	Alive
2R∗	Yes	BLM	AD	Frameshift	c.2506_2507del	p.Arg836Glyfs∗18	NM_000057.4	0.52	LP	71	CMML	MPL p.Ser204Pro TET2 p.Arg544Ter TET2 p.Gln1053Ter	Relapse, death from infection
3R∗	Yes	BLM	AD	Nonsense	c.1642C>T	p.Gln548∗	NM_000057.4	0.43	LP	57	MDS, unclassifiable†	—	Alive
4R∗	Yes	BRCA2	AD	Frameshift	c.5946delT	p.Ser1982Argfs∗22	NM_000059.4	0.51	P	52	RAEB-1†	RAD50 p.Asn934Lysfs TP53 p.Lys132Glu	Relapse, death from primary disease
5R∗	Yes	BRCA2	AD	Frameshift	c.5946delT	p.Ser1982Argfs∗22	NM_000059.4	0.58	P	59	RCMD†	—	Relapse, death from primary disease
6R∗	Yes	BRCA2	AD	Nonsense	c.5217_5223del	p.Tyr1739∗	NM_000059.4	0.61	P	56	RAEB-2	TP53 c.783-1G>A PPM1D p.Val465Aspfs SMC1A p.Lys752Argfs	Relapse, death from primary disease
7R∗	Yes	BRIP1	AD	Frameshift	c.1236delA	p.Val413Phefs∗10	NM_032043.3	0.53	LP	63	RAEB-2	—	Relapse, death from infection
8R∗	Yes	BRIP1	AD	Frameshift	c.3196delT	p.Ser1066Hisfs∗12	NM_032043.3	0.45	LP	64	MDS, unclassifiable†	CBL p.Cys404Tyr DNMT3A p.Arg882His NRAS p.Gly12Asp SETBP1 p.Asp868Asn ASXL1 p.Tyr591Ter	Relapse, death from primary disease
9R∗	Yes	BRIP1	AD	Frameshift	c.2392C>T	p.Arg798∗	NM_032043.3	0.69	LP	60	RAEB-2	NF1 c.3198-1G>T	Relapse, death from primary disease
10R∗	Yes	CHEK2	AD	Frameshift	c.1229del	p.Thr410Metfs∗15	NM_001005735.2	0.39	P	49	MDS, unclassifiable	—	Relapse, alive
11R∗	Yes	CHEK2	AD	Frameshift	c.1392delT	p.Ser465Valfs∗15	NM_001005735.2	0.53	LP	54	MDS associated with isolated del(5q)	NFE2 p.Arg323Alafs CSNK1A1 p.Asp140Ala	Alive
12R	No	DDX41	AD	Nonsense	c.415_418dup	p.Asp140Glyfs∗2	NM_016222.4	0.43	P	66	MDS, unclassifiable	ASXL1 p.Gly646Trpfs	Alive
13R	No	DDX41	AD	Nonsense	c.415_418dup	p.Asp140Glyfs∗2	NM_016222.4	0.49	P	57	RAEB-2	—	Alive
14R∗	Yes	DDX41	AD	Nonsense	c.415_418dup	p.Asp140Glyfs∗2	NM_016222.4	0.42	P	49	RAEB-2	—	Alive
15R	No	DDX41	AD	Frameshift	c.155dupA	p.Arg53Alafs∗16	NM_016222.4	0.49	P	69	RAEB-2	—	Relapse, death from primary disease
16R	Yes	ERCC6L2	AR	Nonsense	c.19C>T	p.Gln7∗	NM_001010895.4	1	LP	34	RAEB-1	SF3B1 p.Arg238Cys TP53 p.Arg175His	Relapse, death from primary disease
17R	Yes	FANCA	AR	Indel	c.3791_3793del	p.Ser1264del	NM_000135.4	1	P	11	RAEB-2	—	Nonrelapse mortality, cause of death not specified
18R	Yes	FANCG	AR	Frameshift	c.907_908dup	p.Glu304Trpfs∗4	NM_004629.2	0.93	LP	27	RA	ASXL1 p.Arg693Ter	Alive
19R∗	Yes	MRE11	AD	Nonsense	c.1516G>T	p.Glu506∗	NM_005591.4	0.54	LP	54	RCMD†	—	Death from infection
20R∗	Yes	MSH6	AD	Frameshift	c.1634_1635del	p.Lys545Argfs∗17	NM_000179.3	0.46	P	49	RA†	—	Nonrelapse mortality, death from secondary malignancy
21R∗	Yes	NBN	AD	Splicing	c.2071-1G>A	na	NM_002485.5	0.62	P	55	CMML	TET2 p.His667Ilefs GATA2 p.Met388_Lys389del RUNX1 p.Leu161_Arg162insSer CBL p.Leu380Pro SRSF2 p.Pro95Leu TET2 p.Lys875Ter	Primary graft failure/rejection, alive
22R∗	Yes	PALB2	AD	Copy number variant	na‡	na	NC_000016.10	0.52	LP	65	RAEB-2	—	Relapse, death from primary disease
23R∗	Yes	PMS2	AD	Nonsense	c.11C>G	p.Ser4∗	NM_001322015.2	0.41	LP	60	RCMD	—	Nonrelapse mortality, death from GVHD
24R	Yes/no§	SBDS	AR	Nonsense/splicing	c.184A>T/c.258+2T>C	p.Lys62∗/na	NM_016038.4	0.38/0.43	P/P	18	RAEB-2	—	Relapse, death from primary disease
25R	Yes/no§	SBDS	AR	Splicing/splicing	c.258+1G>C/c.258+2T>C	na/na	NM_016038.4	0.7/0.26	P/P	19	MDS associated with isolated del(5q)	TP53 c.559+1G>A	Alive
26R∗	Yes	TERT	AD	Nonsense	c.951G>A	p.Trp317∗	NM_198253.3	0.43	LP	51	RAEB-2	—	Alive
27R∗	Yes	TERT	AD	Nonsynonymous	c.193C>G	p.Pro65Ala	NM_198253.3	0.63	LP	64	RAEB-2	TP53 p.Arg248Gln TP53 p.Thr125Thr	Relapse, death from primary disease
28R∗	Yes	TNFRSF13B	AD	Frameshift	c.204dupA	p.Leu69Thrfs∗12	NM_012452.3	0.46	P	66	MDS, unclassifiable	—	Relapse, alive

ACMG, American College of Medical Genetics and Genomics; AD, autosomal dominant; AMP, Association for Molecular Pathology; AR, autosomal recessive; GVHD, graft-versus-host disease; indel, insertion/deletion; na, not applicable; VAF, variant allele frequency; WHO, World Health Organization. Other abbreviations are explained in Table 1.

∗

Donor shares AD germ line variant.

†

Therapy related.

‡

NC_000016.10:g.(?_23607316)_(23641590_?)del.

Donor only shares 1 of the variants in the heterozygous state.

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