Table 2.

Heterozygous germline RECQL4 LOF variants detected in pediatric sequencing cohorts

Subject ID	Cancer diagnosis	Age at diagnosis	Ethnicity of subject	Gene	Chr	Location (hg38)	Exon	HGVS DNA	HGVS protein	Variant class			Variant allele frequency	Coverage	dbSNP ID	Clinical significance in ClinVar	AF in gnomad noncancer v2.1	Ethnicity-specific AF in gnomAD noncancer v2.1	Cohort
											WGS variant allele frequency	WES coverage
SJCNS044968	Craniopharyngioma	5	NFE	RECQL4	8	144,516,696	5	c.423delG	p.Lys141Asnfs*39	Frameshift	0.294	34	NA	NA	-	-	NA	NA	SJCRH
SJALL016422	Acute B-lymphoblastic leukemia	NA	NFEb	RECQL4	8	144,516,254	5	c.865delG	p.Ala289Leufs*4	Frameshift	NA	NA	0.687	32	-	-	NA	NA	TARGET
SJALL019720	Acute lymphoblastic leukemia, NOS	11	NFE	RECQL4	8	144,516,248	5	c.871delG	p.Ala291Leufs*2	Frameshift	0.409	22	0.545	33	rs1389647533	P	4.28 × 10−06	9.85 × 10−06	SJCRH
SJALL015934	Acute B-lymphoblastic leukemia	NA	SASb	RECQL4	8	144,515,890	7	c.1132-2A>G	p.Ala378_E6splice	Splice	NA	NA	0.510	249	-	-	4.29 × 10−06	3.28 × 10−05	TARGET
SJALL019022	Acute B-lymphoblastic leukemia	3	NFE	RECQL4	8	144,515,243	7	c.1391-1G>A	p.Glu464_E8splice	Splice	0.423	26	0.750	16	rs117642173	P	2.89 × 10−05	6.59 × 10−05	SJCRH
SJAML007029	Acute myeloid leukemia	11	NFE	RECQL4	8	144,514,983	9	c.1573delT	p.Cys525Alafs*33	Frameshift	0.567	30	0.550	20	rs386833845	P	2.43 × 10−04	4.21 × 10−04	SJCRH
SJOS019534	Osteosarcoma	6	NFE	RECQL4	8	144,514,983	9	c.1573delT	p.Cys525Alafs*33	Frameshift	0.355	31	0.429	28	rs386833845	P	2.43 × 10−04	4.21 × 10−04	SJCRH
SJCBF029	Acute myelogeneous leukemia	11	NFE	RECQL4	8	144,514,983	9	c.1573delT	p.Cys525Alafs*33	Frameshift	NA	NA	0.571	28	rs386833845	P	2.43 × 10−04	4.21 × 10−04	SJCRH
SJBALL030048	Acute B-lymphoblastic leukemia	3	NFEc	RECQL4	8	144,514,983	9	c.1573delT	p.Cys525Alafs*33	Frameshift	0.218	64	0.315	200	rs386833845	P	2.43 × 10−04	4.21 × 10−04	SJCRH
SJOS030129a	Osteosarcoma	8	AMRc	RECQL4	8	144,514,983	9	c.1573delT	p.Cys525Alafs*33	Frameshift	NA	NA	0.277	90	rs386833845	P	2.43 × 10−04	1.42 × 10−04	SJCRH
SJALL041208	Acute B-lymphoblastic leukemia	4	NFE	RECQL4	8	144,514,983	9	c.1573delT	p.Cys525Alafs*33	Frameshift	0.4	30	0.470	66	rs386833845	P	2.43 × 10−04	2.43 × 10−04	SJCRH
SJGCT041514	Germ cell tumor, testicular	0.3	NFE	RECQL4	8	144,514,983	9	c.1573delT	p.Cys525Alafs*33	Frameshift	0.364	44	0.473	55	rs386833845	P	2.43 × 10−04	2.43 × 10−04	SJCRH
SJBALL002191	Acute B-lymphoblastic leukemia	NA	NFEb	RECQL4	8	144,514,983	9	c.1573delT	p.Cys525Alafs*33	Frameshift	NA	NA	0.293	58	rs386833845	P	2.43 × 10−04	2.43 × 10−04	TARGET
SJTALL022098	Acute T-lymphoblastic leukemia	10	AMRb	RECQL4	8	144,514,983	9	c.1573delT	p.Cys525Alafs*33	Frameshift	NA	NA	0.545	11	rs386833845	P	2.43 × 10−04	1.44 × 10−04	TARGET
SJHL019300	Hodgkin lymphoma	7	AFR	RECQL4	8	144,514,363	10	c.1705-1delG	p.Ile569_E11splice	Splice	0.364	44	0.500	10	-	-	NA	NA	SJCRH
SJST030131	Spindle cell sarcoma	16	AFRc	RECQL4	8	144,514,350	11	c.1717C>T	p.Gln573*	Nonsense	0.275	58	0.25	8	-	-	3.19 × 10−05	1.15 × 10−04	SJCRH
SJTALL065	Acute T-lymphoblastic leukemia	8	AFR	RECQL4	8	144,513,592	13	c.2178_ 2179insCCTGGGTC	p.Ala727Profs*119	Frameshift	NA	NA	0.2	73	-	-	NA	NA	SJCRH
SJOS040215	Osteosarcoma	NA	NFEb	RECQL4	8	144,513,412	14	c.2269C>T	p.Gln757*	Nonsense	NA	NA	0.503	153	rs137853229	P	1.24 × 10−04	1.45 × 10−04	TARGET
SJOS040163	Osteosarcoma	NA	NFEb	RECQL4	8	144,513,383	15	c.2296+1C>G	p.Arg766_E15splice	Splice	NA	NA	0.357	26	rs199605511	-	NA	NA	TARGET
SJNHL019456	Non-Hodgkin lymphoma	7	NFE	RECQL4	8	144,513,109	16	c.2492_2493delAT	p.His831Argfs*52	Frameshift	0.263	19	0.064	47	rs752729755	P	7.02 × 10−05	7.01 × 10−05	SJCRH
SJHL042013	Hodgkin lymphoma	18	NFE	RECQL4	8	144,513,109	16	c.2492_2493delAT	p.His831Argfs*52	Frameshift	0.5	34	0.400	5	rs752729755	P	7.02 × 10−05	7.01 × 10−05	SJCRH
SJOS040168	Osteosarcoma	NA	NFEb	RECQL4	8	144,512,846	16	c.2755+1G>A	p.Ala919_E16splice	Splice	NA	NA	0.316	19	rs373130543	-	3.16 × 10−05	2.86 × 10−05	TARGET
SJALL019726	Acute B-lymphoblastic leukemia	3	NFE	RECQL4	8	144,513,109	19	c.3073_3074delAG	p.Thr1024_Glu1025fs	Frameshift	0.44	25	0.385	39	-	-	NA	NA	SJCRH
SJRB001130	Retinoblastoma	NA	OTH	RECQL4	8	144,511,911	20	c.3393+2T>G	p.Arg1131_E20splice	Splice	0.6	15	NA	NA	rs557284122	-	1.52 × 10−05	0.00 × 10+00	SJCRH

All ethnicities were computationally predicted unless otherwise noted. All predicted populations were consistent with self-reporting unless otherwise noted.

(LOF) Loss of function, (WGS) whole-genome sequencing, (WES) whole-exome sequencing.

^aIndex case.

^bSelf-reporting not available.

^cSelf-reported ethnicity only.