Table 1.

Classification of pathogenicity for 21 germline variants using ACMG-AMP guidelines

Patient IDCohortAncestryGenomic locationHGNC_ symbolAML VAF, germline VAFdbSNP IDVariantACMG-AMP classificationDescription of classification
PATABB TARGET European 11:108199929 ATM 0.38, 0.48 rs28904921 p.Val2424Gly/c.7271T>G Likely pathogenic PS3 moderate, PM1 moderate, PP3 supporting, PP5 strong, BS1 strong 
PASRTP TARGET American 17:59760675 BRIP1 0.44, 0.47 rs730881646 p.Met1244fs/c.3730_3731delAT Likely benign BS1 strong 
PATJMY TARGET European 17:8138449 CTC1 0.54, 0.5 rs748852501 p.Glu454fs/c.1360delG VUS PVS1 very strong, BS1 supporting 
PAMYMA TARGET European 5:34945846 DNAJC21 0.42, 0.54 rs369359554 p.Arg388*/c.1162C>T VUS PVS1 very strong, BS1 supporting 
PARBTV TARGET European 2:25457242 DNMT3A 0.46, 0.52 rs147001633 p.Arg882His/c.2645G>A Likely pathogenic PM1 moderate, PM5 moderate, PS3 moderate, PP2 supporting, PP3 supporting, PP5 supporting, BS1 supporting. 
PARZIA TARGET Asian 2:25468174 DNMT3A 0.56, 0.31 rs149738328 p.Asn501Ser/c.1502A>G Likely benign PM1 moderate, PP2 supporting, BS1 strong, BP4 supporting, BP6 supporting 
PAMXZY TARGET European 17:17119708 FLCN 0.4, 0.4 rs80338682 p.His429fs/c.1285delC Pathogenic PVS1 very strong, PP3 supporting, PP5 strong, BS1 supporting 
PASCGC TARGET Asian 13:20763351 GJB2 0.46, 0.51 rs397516874 p.Gln124*/c.370C>T Pathogenic PVS1 strong, PP3 supporting, PP5 strong, BS1 supporting 
PARZIA TARGET Asian 13:20763529 GJB2 0.64, 0.41 rs750188782 p.Gly59fs/c.176_191delGC
TGCAAGAACGTGTG 		Pathogenic PVS1 strong, PP3 supporting, PP5 strong, BS1 strong 
13.3 Australian European 7:151947936 KMT2C 0.65, NA NA c.1735 + 2T>C Pathogenic PVS1 very strong, PM2 moderate, PP3 supporting 
19.3 Australian Asian 17:29553477 NF1 0.45, NA rs587781807 p.Ile679fs/c.2033dupC Pathogenic PVS1 very strong, PP3 supporting, PP5 supporting, BS1 supporting, 
19.3 Australian Asian 17:29676260 NF1 0.41, NA NA p.Tyr2438fs/c.7313dupA Pathogenic PVS1 very strong, PM2 moderate 
PASSLT TARGET American 5:131915553 RAD50 0.47, 0.59 NA c.552-1G>A Pathogenic PVS1 very strong, PM2 supporting, PP3 supporting, PP5 supporting 
PATELT TARGET European 21:36171704 RUNX1 0.53, 0.49 rs121912499 p.Tyr287*/c.861C>A Pathogenic Classified as pathogenic by the ClinGen Myeloid Malignancy Variant Curation Expert Panel 
PAKKBK TARGET European 21:36252865 RUNX1 0.47, 0.49 rs1060499616 p.Arg166Gln/c.497G>A Pathogenic Classified as pathogenic by the ClinGen Myeloid Malignancy Variant Curation Expert Panel 
PARXYR TARGET European 16:3639742 SLX4 0.59, 0.56 rs763914156 p.Arg1299fs/c.3895_3896del
AG 		VUS PVS1 very strong, BS1 supporting 
14.3 Australian European 15:38643503 SPRED1 0.35, NA rs1057518683 p.Arg325*/c.973C>T Likely pathogenic PVS1 strong, PM2 moderate, PP3 supporting, PP5 supporting 
PATELT TARGET European 4:106197552 TET2 0.33, 0.42 rs200971953 p.Pro1983Leu/c.5948C>T VUS PP3 supporting, BS1 strong 
24.3 Australian European 17:7579689 TP53 0.92, NA NA p.Val31fs/c.90_96 + 10delCGT
TCTGGTAAGGACAA 		Pathogenic PVS1 very strong PM2 moderate, PP3 supporting 
5.3 Australian European 11:32417942 WT1 0.36, NA NA p.Val371fs/c.1109_1110insC Pathogenic PVS1 very strong PM2 moderate, PP3 supporting 
PASYEJ TARGET European 7:152357810 XRCC2 0.45, 0.5 rs730882048 p.Phe32fs/c.96delT Pathogenic PVS1 very strong, PM2 moderate, PP3 supporting, PP5 supporting 
Patient IDCohortAncestryGenomic locationHGNC_ symbolAML VAF, germline VAFdbSNP IDVariantACMG-AMP classificationDescription of classification
PATABB TARGET European 11:108199929 ATM 0.38, 0.48 rs28904921 p.Val2424Gly/c.7271T>G Likely pathogenic PS3 moderate, PM1 moderate, PP3 supporting, PP5 strong, BS1 strong 
PASRTP TARGET American 17:59760675 BRIP1 0.44, 0.47 rs730881646 p.Met1244fs/c.3730_3731delAT Likely benign BS1 strong 
PATJMY TARGET European 17:8138449 CTC1 0.54, 0.5 rs748852501 p.Glu454fs/c.1360delG VUS PVS1 very strong, BS1 supporting 
PAMYMA TARGET European 5:34945846 DNAJC21 0.42, 0.54 rs369359554 p.Arg388*/c.1162C>T VUS PVS1 very strong, BS1 supporting 
PARBTV TARGET European 2:25457242 DNMT3A 0.46, 0.52 rs147001633 p.Arg882His/c.2645G>A Likely pathogenic PM1 moderate, PM5 moderate, PS3 moderate, PP2 supporting, PP3 supporting, PP5 supporting, BS1 supporting. 
PARZIA TARGET Asian 2:25468174 DNMT3A 0.56, 0.31 rs149738328 p.Asn501Ser/c.1502A>G Likely benign PM1 moderate, PP2 supporting, BS1 strong, BP4 supporting, BP6 supporting 
PAMXZY TARGET European 17:17119708 FLCN 0.4, 0.4 rs80338682 p.His429fs/c.1285delC Pathogenic PVS1 very strong, PP3 supporting, PP5 strong, BS1 supporting 
PASCGC TARGET Asian 13:20763351 GJB2 0.46, 0.51 rs397516874 p.Gln124*/c.370C>T Pathogenic PVS1 strong, PP3 supporting, PP5 strong, BS1 supporting 
PARZIA TARGET Asian 13:20763529 GJB2 0.64, 0.41 rs750188782 p.Gly59fs/c.176_191delGC
TGCAAGAACGTGTG 		Pathogenic PVS1 strong, PP3 supporting, PP5 strong, BS1 strong 
13.3 Australian European 7:151947936 KMT2C 0.65, NA NA c.1735 + 2T>C Pathogenic PVS1 very strong, PM2 moderate, PP3 supporting 
19.3 Australian Asian 17:29553477 NF1 0.45, NA rs587781807 p.Ile679fs/c.2033dupC Pathogenic PVS1 very strong, PP3 supporting, PP5 supporting, BS1 supporting, 
19.3 Australian Asian 17:29676260 NF1 0.41, NA NA p.Tyr2438fs/c.7313dupA Pathogenic PVS1 very strong, PM2 moderate 
PASSLT TARGET American 5:131915553 RAD50 0.47, 0.59 NA c.552-1G>A Pathogenic PVS1 very strong, PM2 supporting, PP3 supporting, PP5 supporting 
PATELT TARGET European 21:36171704 RUNX1 0.53, 0.49 rs121912499 p.Tyr287*/c.861C>A Pathogenic Classified as pathogenic by the ClinGen Myeloid Malignancy Variant Curation Expert Panel 
PAKKBK TARGET European 21:36252865 RUNX1 0.47, 0.49 rs1060499616 p.Arg166Gln/c.497G>A Pathogenic Classified as pathogenic by the ClinGen Myeloid Malignancy Variant Curation Expert Panel 
PARXYR TARGET European 16:3639742 SLX4 0.59, 0.56 rs763914156 p.Arg1299fs/c.3895_3896del
AG 		VUS PVS1 very strong, BS1 supporting 
14.3 Australian European 15:38643503 SPRED1 0.35, NA rs1057518683 p.Arg325*/c.973C>T Likely pathogenic PVS1 strong, PM2 moderate, PP3 supporting, PP5 supporting 
PATELT TARGET European 4:106197552 TET2 0.33, 0.42 rs200971953 p.Pro1983Leu/c.5948C>T VUS PP3 supporting, BS1 strong 
24.3 Australian European 17:7579689 TP53 0.92, NA NA p.Val31fs/c.90_96 + 10delCGT
TCTGGTAAGGACAA 		Pathogenic PVS1 very strong PM2 moderate, PP3 supporting 
5.3 Australian European 11:32417942 WT1 0.36, NA NA p.Val371fs/c.1109_1110insC Pathogenic PVS1 very strong PM2 moderate, PP3 supporting 
PASYEJ TARGET European 7:152357810 XRCC2 0.45, 0.5 rs730882048 p.Phe32fs/c.96delT Pathogenic PVS1 very strong, PM2 moderate, PP3 supporting, PP5 supporting 

See supplemental Methods for more details.

NA, not available; VUS, variant of uncertain significance.

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