Table 2.

ITGA2B/ITGB3 variants with discordant initial and final classifications

GenecDNAAmino acidClinVar assertionInitial expert assertionFinal PD-EP classificationCriteria applied
ClinVar/initial assertion conflicting       
 ITGA2B 3060+2T>C  VUS Pathogenic Likely pathogenic PVS1_S, PM2_P, PM3_P, PP4_M 
 ITGA2B 2965G>A Ala989Thr VUS Likely benign Likely benign BS1, BP2, BP4 
 ITGA2B 891+12del  VUS Benign Benign BA1, BP7 
 ITGB3 565C>T Pro189Ser Likely pathogenic VUS Pathogenic PS3_M, PM2_P, PM3_S, PP1, PP3, PP4 
 ITGB3 1960G>A Glu654Lys VUS and likely benign VUS Benign BA1 
 ITGB3 1902C>T Cys634= Likely benign VUS Benign BA1, BP7 
Reclassified from VUS       
 ITGA2B 1234G>A Gly412Arg VUS VUS Pathogenic PM2_P, PM3_S, PP3, PP4_S 
 ITGA2B 257T>C Leu86Pro N/A VUS Pathogenic PS3_M, PM2, PM3_P, PP3, PP4_S 
 ITGA2B 460_462del Glu154del N/A VUS Likely pathogenic PM2_P, PM3_P, PM4, PP4_M 
 ITGB3 362-1G>A  VUS VUS Likely pathogenic PVS1, PM2_P 
 ITGB3 187C>T Arg63Cys VUS VUS Likely pathogenic PS3_M, PM2_P, PM3_P, PP3, PP4_M 
 ITGB3 448A>G Met150Val N/A VUS Likely pathogenic PM2_P, PM3, PP3, PP4_M 
 ITGB3 629G>C Cys210Ser N/A VUS Likely pathogenic PS3, PM2_P, PP1, PP3, PP4_M 
 ITGB3 1458C>G Cys486Trp N/A VUS Likely pathogenic PM2_P, PM3, PP3, PP4_S 
 ITGB3 1594T>C Cys532Arg N/A VUS Likely pathogenic PM2_P, PM3, PP3, PP4_S 
 ITGB3 1595G>A Cys532Tyr N/A VUS Likely pathogenic PM2_P, PM3_P, PM5_P, PP3, PP4_M 
Reclassified to VUS       
 ITGA2B 2852_2853delinsC Asp951AlafsTer? N/A Likely pathogenic VUS PVS1_S, PM2_P 
 ITGA2B 889G>C Ala297Pro N/A Likely pathogenic VUS PM2_P, PM3_P, PP1, PP4_M 
 ITGA2B 1821G>A Thr607= Likely benign Likely benign VUS PP3 
 ITGA2B 2728-19T>C  N/A Likely benign VUS BP7, PM2_P 
 ITGB3 1366A>C Thr456Pro Likely pathogenic Pathogenic VUS PM2_P, PM3_P 
 ITGB3 953 T>C Leu318Ser N/A Likely pathogenic VUS PM2_P, PM3_P, PP3, PP4_M 
 ITGB3 1125+29G>C  N/A Benign VUS BP7, PM2_P 
GenecDNAAmino acidClinVar assertionInitial expert assertionFinal PD-EP classificationCriteria applied
ClinVar/initial assertion conflicting       
 ITGA2B 3060+2T>C  VUS Pathogenic Likely pathogenic PVS1_S, PM2_P, PM3_P, PP4_M 
 ITGA2B 2965G>A Ala989Thr VUS Likely benign Likely benign BS1, BP2, BP4 
 ITGA2B 891+12del  VUS Benign Benign BA1, BP7 
 ITGB3 565C>T Pro189Ser Likely pathogenic VUS Pathogenic PS3_M, PM2_P, PM3_S, PP1, PP3, PP4 
 ITGB3 1960G>A Glu654Lys VUS and likely benign VUS Benign BA1 
 ITGB3 1902C>T Cys634= Likely benign VUS Benign BA1, BP7 
Reclassified from VUS       
 ITGA2B 1234G>A Gly412Arg VUS VUS Pathogenic PM2_P, PM3_S, PP3, PP4_S 
 ITGA2B 257T>C Leu86Pro N/A VUS Pathogenic PS3_M, PM2, PM3_P, PP3, PP4_S 
 ITGA2B 460_462del Glu154del N/A VUS Likely pathogenic PM2_P, PM3_P, PM4, PP4_M 
 ITGB3 362-1G>A  VUS VUS Likely pathogenic PVS1, PM2_P 
 ITGB3 187C>T Arg63Cys VUS VUS Likely pathogenic PS3_M, PM2_P, PM3_P, PP3, PP4_M 
 ITGB3 448A>G Met150Val N/A VUS Likely pathogenic PM2_P, PM3, PP3, PP4_M 
 ITGB3 629G>C Cys210Ser N/A VUS Likely pathogenic PS3, PM2_P, PP1, PP3, PP4_M 
 ITGB3 1458C>G Cys486Trp N/A VUS Likely pathogenic PM2_P, PM3, PP3, PP4_S 
 ITGB3 1594T>C Cys532Arg N/A VUS Likely pathogenic PM2_P, PM3, PP3, PP4_S 
 ITGB3 1595G>A Cys532Tyr N/A VUS Likely pathogenic PM2_P, PM3_P, PM5_P, PP3, PP4_M 
Reclassified to VUS       
 ITGA2B 2852_2853delinsC Asp951AlafsTer? N/A Likely pathogenic VUS PVS1_S, PM2_P 
 ITGA2B 889G>C Ala297Pro N/A Likely pathogenic VUS PM2_P, PM3_P, PP1, PP4_M 
 ITGA2B 1821G>A Thr607= Likely benign Likely benign VUS PP3 
 ITGA2B 2728-19T>C  N/A Likely benign VUS BP7, PM2_P 
 ITGB3 1366A>C Thr456Pro Likely pathogenic Pathogenic VUS PM2_P, PM3_P 
 ITGB3 953 T>C Leu318Ser N/A Likely pathogenic VUS PM2_P, PM3_P, PP3, PP4_M 
 ITGB3 1125+29G>C  N/A Benign VUS BP7, PM2_P 

Criteria applied with a modified strength are denoted by the criteria followed by _P for supporting, _M for moderate, _S for strong, and _VS for very strong.

cDNA, complementary DNA; N/A, not applicable.