Table 2 Pathogenic/likely pathogenic variants in autosomal dominant genes or compound heterozygous variants in recessive genes.

From: Enrichment of cancer-predisposing germline variants in adult and pediatric patients with acute lymphoblastic leukemia

Patient	Age	Type	Gene	Inheritance	Germline disease association for gene	ACMG Intervar	ACMG Varsome	Conclusion of pathogenicity	Variant HGVS	gnomAD all MAF	gnomAD Finns MAF
2181	41	B-ALL	BRCA1	AR;AD	Fanconi anemia; Breast cancer	P	P	P	c.4097-2A > G (splicing)	0	0
2150	32	B-ALL	CHEK2	AD	Li-Fraumeni syndrome 2	VUS	P	P	c.1100del (p.Thr367MetfsTer15)	0.00205	0.00874
2149	43	B-ALL	PMS2	AR;AD	CMMRD; HNPCC	P	P	P	c.765C > A (p.Tyr255Ter)	0	0
2307*	53	T-ALL	RET	AD	Multiple endocrine neoplasia	VUS	P	P	c.2410G > A (p.Val804Met)	0.00011	0
2167	54	T-ALL	RUNX1	AD	Familial platelet disorder with predisposition to AML	LP	P	P	c.611G > A (p.Arg204Gln)	0	0
2307*	53	T-ALL	SDHB	AD	Familial paraganglioma-pheochromocytoma	VUS	LP	LP	c.177G > C (p.Gln59His)	0.000004	0
P2220^†	8	Ph-ALL	BRIP1	AR;AD	FA; Breast cancer	VUS	P	LP	c.3440dup (p.Asn1147LysfsTer2)	0.00009	0.00068
P2206	15	B-ALL	CHEK2	AD	Li-Fraumeni syndrome 2	VUS	P	P	c.1100del (p.Thr367MetfsTer15)	0.00205	0.00874
P2209^†	15	B-ALL	CHEK2	AD	Li-Fraumeni syndrome 2	VUS	P	P	c.1100del (p.Thr367MetfsTer15)	0.00205	0.00874
P2249*	2	T-ALL	CHEK2	AD	Li-Fraumeni syndrome 2	VUS	P	P	c.1100del (p.Thr367MetfsTer15)	0.00205	0.00874
P2257^†	14	T-ALL	CHEK2	AD	Li-Fraumeni syndrome 2	VUS	P	P	c.1100del (p.Thr367MetfsTer15)	0.00205	0.00874
P2431	9	T-ALL	CHEK2	AD	Li-Fraumeni syndrome 2	VUS	P	P	c.1100del (p.Thr367MetfsTer15)	0.00205	0.00874
P2249*	2	T-ALL	LZTR1	AR/AD;AD	Noonan syndrome, Schwannomatosis	P	P	LP	c.2407-1G > A (splicing)	0.00002	0.00018
P2216*	8	T-ALL	MUTYH	AR	Familial adenomatous polyposis	LP	P	P	c.1187G > A (p.Gly396Asp)	0.00295	0.0022
P2216*	8	T-ALL	MUTYH	AR	Familial adenomatous polyposis	LP	P	P	c.536A > G (p.Tyr179Cys)	0.00154	0.00153
P2255	0	B-ALL	PMS2	AR;AD	CMMRD; HNPCC	P	P	P	c.325dup (p.Glu109GlyfsTer30)	0.00002	0
P2261	0	B-ALL	SDHC	AD	Familial paraganglioma-pheochromocytoma	LP	P	LP	c.380A > G (p.His127Arg)	0	0
P2224	2	B-ALL	TP53	AD	Li-Fraumeni syndrome	LP	P	P	c.733G > A (p.Gly245Ser)	0	0
						Total P/LP 10 variants,9 patients^a	Total P/LP 20 variants, 17 patients^a	Total P/LP 18 variants, 15 patients

ACMG, American College of Medical Genetics; AD, autosomal dominant; AML, acute myeloid leukemia; AR, autosomal recessive; B-ALL, Ph-negative B-ALL; Ph-ALL, Ph-positive B-ALL; CMMRD, constitutional mismatch repair deficiency; FA, Fanconi anemia; HNPCC, hereditary non-polyposis colorectal cancer; LP, likely pathogenic; MAF, minor allele frequency; P, pathogenic; VUS, variant of uncertain significance.
*Patients with multiple P/LP variants.
^†Samples with a high blast percentage.
^aAll variants classified P/LP by Intervar and Varsome not shown here. Pediatric patients are marked with a P.

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Table 2 Pathogenic/likely pathogenic variants in autosomal dominant genes or compound heterozygous variants in recessive genes.

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