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Table 2 Prioritized variants identified in the HBOC cohort and its pathogenicity prediction

From: Germline variants in DNA repair genes associated with hereditary breast and ovarian cancer syndrome: analysis of a 21 gene panel in the Brazilian population

GeneVariant nomenclaturedbSNP IDVariant typeVarsomeClinVarIn silico PredictionsSample ID
Coding DNAProteinCADDAlignGVGDUMD PREDICTORSIFTPolyPhenMutation Taster
HR genes
ATMc.1541G > Ap.Gly514Asprs2235000missenseBenignBenign/Likely Benign25.7Class C65PolymorphismToleratedProbably damagingDisease Causing3664; 4146
c.1636C > Gp.Leu546Valrs2227924missenseLikely BenignBenign/Likely Benign11.58Class C25PolymorphismDamagingPossibly damagingPolymorphism3617; 3634
c.1810C > Tp.Pro604Serrs2227922missenseUncertain SignificanceBenign/Likely Benign23.3Class C65Probably polymorphismToleratedPossibly damagingDisease Causing2775
c.2442C > Ap.Asp814Glurs3218695missenseLikely BenignBenign15.88Class C35PolymorphismToleratedBenignPolymorphism2753; 2784
c.2572 T > Cp.Phe858Leurs1800056missenseUncertain SignificanceConflicting interpretations of pathogenicity13.50Class C15PolymorphismDamagingPossibly damagingPolymorphism4268
c.4258C > Tp.Leu1420Phers1800058missenseUncertain SignificanceConflicting interpretations of pathogenicity15.47Class C15PolymorphismToleratedBenignDisease Causing3650
c.5557G > Ap.Asp1853Asnrs1801516missenseBenignBenign/Likely Benign23.2Class C15PolymorphismToleratedBenignPolymorphism2699; 2724; 2775; 3002; 3132 (homoz); 3141; 3166; 3187; 3728 (homoz); 4063; 4133; 4135; 4137; 4138 (homoz); 4147; 4226 (homoz)
c.6995 T > Cp.Leu2332Prors4988111missenseLikely BenignBenign/Likely Benign15.87Class C65PolymorphismToleratedBenignPolymorphism3617; 3634
c.7740A > Cp.Arg2580Serrs199915459missenseUncertain SignificanceUncertain significance15.65Class C65PathogenicToleratedBenignDisease Causing3671
c.5558A > Tp.Asp1853Valrs1801673missenseUncertain SignificanceConflicting interpretations of pathogenicity24.2Class C65PathogenicDamagingPossibly damagingDisease Causing4186; 4264
ATRc.2794C > Ap.Pro932ThrmissenseUncertain Significance27.0Class C35PathogenicDamagingProbably damagingDisease Causing4020
c.7300C > Gp.Pro2434Alars33972295missenseLikely BenignBenign/Likely Benign23.5Class C25PolymorphismDamagingProbably damagingDisease Causing4228
c.946G > Ap.Val316Ilers28897764missenseLikely BenignBenign/Likely Benign18.61Class C25Probable polymorphismToleratedBenignDisease Causing2726; 3116; 3671; 3703; 4228
BARD1c.-83C > Trs715798405’UTR premature start codon gainLikely Benign84853002
c.1972C > Tp.Arg658Cysrs3738888missenseUncertain SignificanceBenign/Likely Benign26.5Class C65Probably pathogenicDamagingProbably damagingDisease Causing3671
c.1268A > Gp.Lys423Argrs749383704missenseUncertain SignificanceUncertain significance21.8Class C25Probably pathogenicToleratedBenignDisease Causing2995
c.764A > Gp.Asn255Serrs138904906missenseLikely BenignUncertain significance16.75Class C45PolymorphismToleratedProbably damagingPolymorphism3716
c.716 T > Ap.Leu239Glnrs200359745missenseLikely BenignUncertain significance1061Class C65Probably pathogenicToleratedBenignPolymorphism3051
BRCA1c.*421G > Trs81763183’UTRBenignBenign4.782697 (homoz); 2699; 2742; 2750; 2753; 2779; 2801; 2815; 2972; 2977; 3002; 3056; 3078; 3097; 3114; 3115; 3116; 3132; 3141; 3166; 3227; 3462; 3617; 3671; 3703; 3728; 3806; 3842; 3897; 4016; 4020; 4135; 4138; 4146; 4147; 4161; 4166; 4177; 4220; 4226; 4228; 4279
c.3119G > Ap.Ser1040Asnrs4986852missenseLikely BenignBenign14.86Class C45PolymorphismToleratedProbably damagingPolymorphism2699; 2785; 2995; 3002; 3114; 3876; 4020; 4037; 4132
c.5019G > Ap.Met1673Ilers1799967missenseBenignBenign22.0Class C0Probable polymorphismToleratedBenignDisease Causing3897
c.4598G > Tp.Ser1533Ilers1800744missenseLikely BenignBenign16.14Class C65PolymorphismDamagingPossibly damagingPolymorphism3113
c.1648A > Cp.Asn550Hisrs56012641missenseLikely BenignBenign17.67Class C65PolymorphismDamagingProbably damagingPolymorphism4132
c.1067A > Gp.Gln356Argrs1799950missenseBenignBenign17.80Class C35PolymorphismDamagingProbably damagingPolymorphism2724; 2775; 3187; 3703; 4133; 4139
c.2077G > Ap.Asp693Asnrs4986850missenseBenignBenign15.84Class C15PolymorphismDamagingBenignPolymorphism2815; 2977; 3097; 3116; 3671; 4122; 4220
c.5507G > Ap.Trp1836Terrs80356962stop gainedPathogenicPathogenic44PathogenicDisease Causing3051
c.5329dupCp.Gln1756Profs*74rs397507247frameshiftPathogenicPathogenic352812; 3132; 3141; 3155; 3639; 3722; 3728; 4093; 4135; 4137; 4186
c.3331_3334delCAAGp.Gln1111Asnfs*5rs80357701frameshiftPathogenicPathogenic23.72723
c.2612C > Tp.Pro871Leurs799917missenseBenignBenign17.97Class C65ToleratedBenignPolymorphism2697 (homoz); 2699; 2724; 2726; 2742 (homoz); 2750; 2753; 2779 (homoz); 2801; 2812; 2815; 2972; 2977; 3002; 3056 (homoz); 3078 (homoz); 3083; 3097; 3114; 3115 (homoz); 3116 (homoz); 3132; 3141; 3166; 3227; 3441(homoz); 3462; 3617(homoz); 3650(homoz); 3651; 3664(homoz); 3671; 3703; 3728; 3782; 3802; 3806; 3842(homoz); 3897; 3920; 4016; 4020; 4037; 4063; 4093; 4122; 4135; 4138; 4139; 4144; 4146(homoz); 4147; 4161; 4166 (homoz); 4177; 4186 (homoz); 4214; 4220; 4226 (homoz); 4228; 4250 (homoz); 4262; 4268 (homoz); 4279
c.3548A > Gp.Lys1183Argrs16942missenseBenignBenign Class C25ToleratedBenignPolymorphism2697 (homoz); 2699; 2742; 2750; 2753; 2801; 2815; 2972; 2977; 3002; 3056; 3078 (homoz); 3097; 3114; 3116; 3141; 3166; 3462; 3617 (homoz); 3651; 3703; 3806; 3842 (homoz); 3897; 4016; 4020; 4122; 4135; 4138; 4146; 4161; 4166; 4262; 4268 (homoz); 4279
c.4900A > Gp.Ser1613Glyrs1799966missenseBenignBenign Class C55PolymorphismDamagingPossibly damagingPolymorphism2697; 2699; 2742; 2750; 2753; 2779; 2784; 2801; 2815; 2972; 2977; 3002; 3056; 3078 (homoz); 3097; 3114; 3115; 3116; 3132; 3141; 3166; 3227; 3462; 3617 (homoz); 3651; 3671; 3703; 3728; 3782; 3806; 3842 (homoz); 3897; 4016; 4020; 4122; 4135; 4138; 4146; 4147; 4161; 4166; 4177; 4220; 4226; 4228; 4262; 4268 (homoz); 4279
c.536A > Gp.Tyr179Cysrs56187033missenseLikely BenignBenign24.7Class C65PathogenicDamagingProbably damagingDisease Causing4132
c.591C > Tp.Cys197Cysrs1799965splice regionLikely BenignUncertain significance14.63Probably pathogenic4063
c.3113A > Gp.Glu1038Glyrs16941missenseBenignBenign22.2Class C65PolymorphismDamagingPossibly damagingPolymorphism2697; 2699; 2742; 2750; 2753; 2779; 2784; 2801; 2815; 2972; 2977; 3002; 3056; 3078 (homoz); 3097; 3114; 3115; 3116; 3132; 3141; 3166; 3227; 3462; 3617 (homoz); 3651; 3671; 3703; 3728; 3782; 3806; 3842; 3897; 4016; 4020; 4122; 4135; 4138; 4146; 4147; 4161; 4166; 4220; 4226; 4228; 4262; 4268 (homoz); 4279
BRCA2c.156_157insAluinsertionPathogenicPathogenic 
c.811G > Ap.Gly271Argrs786204274missenseUncertain SignificanceConflicting interpretations of pathogenicity20.6Class C65Probably pathogenicDamagingBenignPolymorphism2977
c.3869G > Ap.Cys1290Tyrrs41293485missenseLikely BenignBenign14.39Class C65Probably pathogenicToleratedBenignPolymorphism3662
c.4258G > Tp.Asp1420Tyrrs28897727missenseLikely BenignBenign15.81Class C65PolymorphismDamagingBenignPolymorphism3649
c.6100C > Tp.Arg2034Cysrs1799954missenseLikely BenignBenign20.4Class C65PolymorphismDamagingPossibly damagingPolymorphism3441; 3617; 4279
c.8149G > Tp.Ala2717Serrs28897747missenseLikely BenignBenign15.38Class C65PolymorphismToleratedPossibly damagingPolymorphism3002
c.8850G > Tp.Lys2950Asnrs28897754missenseUncertain SignificanceConflicting interpretations of pathogenicity22.4Class C65Probable polymorphismDamagingProbably damagingDisease Causing2781
c.865A > Cp.Asn289Hisrs766173missenseBenignBenign17.23Class C65PolymorphismDamagingProbably damagingPolymorphism2995; 3051; 3056; 3651; 3722; 4166
c.2808_2811delACAAp.Ala938Profs*21rs80359351frameshiftPathogenicPathogenic24.34147
c.8851G > Ap.Ala2951Thrrs11571769missenseLikely BenignBenign26.2Class C55PolymorphismDamagingProbably damagingDisease Causing3051
c.9026_9030delATCATp.Tyr3009Serfs*7rs80359741frameshiftPathogenicPathogenic 2785
c.9382C > Tp.Arg3128Terrs80359212stop gainedPathogenicPathogenic48PathogenicDisease Causing4262
c.9976A > Tp.Lys3326Terrs11571833stop gainedLikely BenignBenign36PathogenicDisease Causing3650
c.8324 T > Gp.Met2775Argrs80359073missenseUncertain SignificanceConflicting interpretations of pathogenicity24.1Class C65PathogenicToleratedBenignDisease Causing3116
BRIP1c.3693A > Gp.Ile1231Metrs876659290missenseUncertain SignificanceUncertain significance13.29Class C0PolymorphismDamagingBenignPolymorphism3132; 3728
c.517C > Tp.Arg173Cysrs4988345missenseLikely BenignBenign/Likely Benign24.9Class C65PathogenicDamagingProbably damagingDisease Causing4122; 4173
c.2220G > Tp.Gln740Hisrs45589637missenseLikely BenignUncertain significance12.53Class C15Probably pathogenicDamagingProbably damagingDisease Causing3078
CHEK2c.410G > Ap.Arg137Glnrs368570187missenseLikely BenignLikely Benign16.54Class C35Probable polymorphismToleratedBenignDisease Causing3116
c.480A > Gp.Ile160Metrs575910805missenseUncertain SignificanceConflicting interpretations of pathogenicity22.6Class C0Probable polymorphismDamagingProbably damagingDisease Causing3097
FAM175A/ABRAXAS1c.489G > Tp.Arg163Serrs535462791missenseUncertain Significance22.3Class C65PathogenicToleratedPossibly damagingDisease Causing3187
c.1042G > Ap.Ala348Thrrs12642536missenseBenign13.44Class C55PolymorphismDamagingPossibly damagingPolymorphism2697; 2699; 2723; 2724; 2726; 2742; 2750; 2754 (homoz); 2775; 2779; 2781 (homoz); 2784 (homoz); 2812; 2972; 2977; 3002; 3078; 3097; 3113 (homoz); 3114 (homoz); 3115; 3132 (homoz); 3141 (homoz), 3155 (homoz); 3166 (homoz); 3441; 3462; 3617; 3634; 3639; 3649 (homoz); 3651; 3662; 3706; 3716; 3722; 3728 (homoz); 3761; 3772; 3806; 3876; 3897; 3920; 4016; 4037; 4063; 4093; 4132 (homoz); 4137; 4144; 4145; 4147; 4161; 4166; 4177; 4226 (homoz); 4228; 4250; 4259; 4264; 4279
MRE11c.1011C > Gp.Ser337Argrs115244417missenseLikely BenignBenign21.9Class C65Probable polymorphismToleratedBenignDisease Causing4135
c.2101A > Gp.Met701Valrs1805362missenseLikely BenignBenign/Likely Benign16.49Class C15PolymorphismDamagingBenignDisease Causing3650
NBNc.202 T > Gp.Leu68Valrs1200599843missenseUncertain SignificanceUncertain significance15.95Class C25PolymorphismToleratedBenignDisease Causing2785
c.797C > Tp.Pro266Leurs769420missenseLikely BenignBenign24.6Class C65PolymorphismDamagingProbably damagingDisease Causing3078
PALB2c.2794G > Ap.Val932Metrs45624036missenseLikely BenignBenign/Likely Benign25.3Class C15PolymorphismToleratedProbably damagingDisease Causing3842
c.53A > Gp.Lys18Argrs138789658missenseUncertain SignificanceConflicting interpretations of pathogenicity24.3Class C25PolymorphismDamagingProbably damagingPolymorphism3897; 4037
c.949A > Cp.Thr317Prors587780223missenseLikely BenignUncertain significance4.012Class C35PolymorphismToleratedPossibly damagingPolymorphism4139
RAD51c.164C > Tp.Ala55Valrs145617142missenseUncertain SignificanceUncertain significance23.6Class C55Probable polymorphismToleratedPossibly damagingDisease Causing3116
UIMC1c.43C > Tp.Arg15Trprs13167812missenseUncertain Significance22.5Class C65PolymorphismDamagingProbably damagingPolymorphism2750; 4250
c.1304C > Tp.Pro435Leurs3733876missenseBenign23.8Class C65PolymorphismDamagingProbably damagingPolymorphism2699; 2724; 2754; 2815; 3056; 3083; 3132 (homoz); 3634; 3649; 3671; 3761; 3842; 3920; 4020; 4063 (homoz); 4138; 4173; 4214
MMR genes
MLH1c.306G > Ap.Glu102Glurs63751665splice regionLikely Benignuncertain significance22.4PathogenicDisease Causing4020
c.637G > Ap.Val213Metrs2308317missenseLikely BenignBenign23.9Class C15PolymorphismToleratedPossibly damagingDisease Causing4020
c.1217G > Ap.Ser406Asnrs41294980missenseLikely BenignBenign13.09Class C45PolymorphismToleratedPossibly damagingPolymorphism2963
c.2146G > Ap.Val716Metrs35831931missenseLikely BenignBenign24.4Class C15Probable polymorphismDamagingProbably damagingDisease Causing2754
MSH2c.2500G > Ap.Ala834Thrrs63750757missenseLikely BenignLikely Benign33.00Class C55PathogenicDamagingProbably damagingDisease Causing4214
c.380A > Gp.Asn127Serrs17217772missenseBenignBenign22.7Class C45Probable polymorphismDamagingPossibly damagingDisease Causing3650; 3920; 4146; 4228
c.965G > Ap.Gly322Asprs4987188missenseLikely BenignBenign23.0Class C65Probable polymorphismToleratedPossibly damagingDisease Causing2815; 3113; 3441; 4264
MSH6c.1186C > Gp.Leu396Valrs2020908missenseLikely BenignBenign16.97Class C25PolymorphismToleratedPossibly damagingDisease Causing2699; 2754
c.2633 T > Cp.Val878Alars2020912missenseLikely BenignBenign10.23Class C55PolymorphismToleratedBenignDisease Causing4147
PMS2c.59G > Ap.Arg20Glnrs10254120missenseBenignBenign16.65Class C35PolymorphismToleratedPossibly damagingPolymorphism4146; 2963; 3097; 3116; 3722; 3782; 3806; 4137; 4145; 4220; 4262
c.2374G > Ap.Asp792Asnrs587781265missenseUncertain SignificanceUncertain significance29.8Class C15Probably pathogenicDamagingProbably damagingDisease Causing3802
c.2350G > Ap.Asp784Asnrs143340522missenseUncertain SignificanceUncertain significance27.8Class C15PolymorphismDamagingProbably damagingDisease Causing4264
c.2149G > Ap.Val717Metrs201671325missenseUncertain SignificanceConflicting interpretations of pathogenicity20.7Class C15Probable polymorphismDamagingProbably damagingDisease Causing3116; 3462
c.1866G > Ap.Met622Ilers1805324missenseLikely BenignBenign18.96Class C0PolymorphismToleratedPossibly damagingDisease Causing3772
c.1688G > Tp.Arg563Leurs63750668missenseLikely BenignBenign/Likely Benign10.65Class C65PolymorphismToleratedPossibly damagingPolymorphism2972; 3227; 4016
Other genes
CDH1c.1849G > Ap.Ala617Thrrs33935154missenseLikely BenignConflicting interpretations of pathogenicity15.13Class C55PolymorphismToleratedBenignDisease Causing3664; 4145; 4166
TP53c.1010G > Ap.Arg337Hisrs121912664missenseLikely PathogenicPathogenic22.6Class C25DamagingProbably damagingDisease Causing2699; 3056; 3227; 3662; 4264
c.818G > Ap.Arg273Hisrs28934576missenseLikely PathogenicPathogenic/Likely pathogenic24.0Class C25PathogenicDamagingProbably damagingDisease Causing3227