Several BRCA2 cancer-derived missense mutations within the SEM1 (DSS1)-binding region, which involves the helical domain (HD) between amino acid residues 2457 and 2668, and the oligonucleotide/oligosaccharide-binding domain 1 (OB1) between amino acid residues 2669 and 2800, have been shown to fully or partially affect the interaction of BRCA2 with SEM1, leading to impaired formation of RAD51 foci and defective homologous recombination repair (HRR):
BRCA2 W2626C (partial loss of function, Lee et al. 2021)
BRCA2 I2627F (Lee et al. 2021)
BRCA2 R2659T (partial loss of function, Lee et al. 2021)
BRCA2 E2663V (partial loss of function, Lee et al. 2021)
BRCA2 T2722R (Lee et al. 2021)
BRCA2 D2723G (Lee et al. 2021)
BRCA2 D2723H (Lee et al. 2021)
BRCA2 G2748D (partial loss of function, Lee et al. 2021).
All these missense mutants of BRCA2 primarily localize to the cytosol (Lee et al. 2021). Two BRCA2 mutations that affect the SEM1-binding region, BRCA2 T2515I and BRCA2 K2729N, are benign and do not impair SEM1 binding (Lee et al. 2021).

In accordance with the standards for interpretation of sequence variants issued by the American College of Medical Genetics and Genomics and the Association for Molecular Pathology, the following missense mutants of BRCA2, reported in cancer, are annotated as candidates for the loss of SEM1 binding ability based on the criterion PM5 (novel missense change at an amino acid residue where a different missense change determined to be pathogenic has been seen before) for moderate evidence of pathogenicity (Richards et al. 2015):
BRCA2 W2626L
BRCA2 E2663Q
BRCA2 T2722I.

BRCA2 nonsense mutants, frameshift insertion mutants, and frameshift deletion mutants listed below have not been functionally studied, except for the BRCA2 F2058Lfs*12 (c.6174delT), a common cancer mutant known to be exclusively cytosolic (Spain et al. 1999). They are annotated as candidate SEM1 binding defective mutants based on the fact that they lack the entire SEM1-binding region between amino acid residues 2457-2800 of BRCA2 (that is, the truncation occurs before the amino acid residue 2457). Based on the standards and guidelines for the interpretation of sequence variants issued by the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (Richards et al. 2015), these mutants satisfy the criterion PM1 for the moderate evidence of pathogenicity (mutations located in a mutational hotspot and/or critical and well-established functional domain without benign variation).

The following BRCA2 nonsense mutants lack the HD and OB1 domains involved in SEM1 binding:
BRCA2 G4*
BRCA2 W31*
BRCA2 Q73*
BRCA2 S76*
BRCA2 E97*
BRCA2 L105*
BRCA2 G106*
BRCA2 K178*
BRCA2 E187*
BRCA2 K230*
BRCA2 E294*
BRCA2 E305*
BRCA2 S353*
BRCA2 Q373*
BRCA2 G405*
BRCA2 E409*
BRCA2 K467*
BRCA2 E475*
BRCA2 Q499*
BRCA2 E510*
BRCA2 L553*
BRCA2 G561*
BRCA2 K604*
BRCA2 Q609*
BRCA2 S611*
BRCA2 L638*
BRCA2 S648*
BRCA2 E654*
BRCA2 C711*
BRCA2 S744*
BRCA2 Q754*
BRCA2 Y803*
BRCA2 E808*
BRCA2 E826*
BRCA2 E865*
BRCA2 E866*
BRCA2 S871*
BRCA2 E880*
BRCA2 Q893*
BRCA2 E897*
BRCA2 G904*
BRCA2 K944*
BRCA2 G995*
BRCA2 G1006*
BRCA2 S1013*
BRCA2 Q1063*
BRCA2 S1064*
BRCA2 K1082*
BRCA2 S1099*
BRCA2 E1113*
BRCA2 E1120*
BRCA2 G1122*
BRCA2 Q1124*
BRCA2 Q1175*
BRCA2 L1208*
BRCA2 S1271*
BRCA2 E1276*
BRCA2 E1285*
BRCA2 S1385*
BRCA2 Q1429*
BRCA2 E1441*
BRCA2 S1442*
BRCA2 Q1452*
BRCA2 K1453*
BRCA2 E1493*
BRCA2 E1514*
BRCA2 K1515*
BRCA2 E1518*
BRCA2 Q1551*
BRCA2 E1555*
BRCA2 Q1562*
BRCA2 E1581*
BRCA2 E1593*
BRCA2 S1630*
BRCA2 E1646*
BRCA2 K1649*
BRCA2 Q1658*
BRCA2 E1688*
BRCA2 Y1714*
BRCA2 E1717*
BRCA2 S1720*
BRCA2 L1740*
BRCA2 Y1762*
BRCA2 E1812*
BRCA2 K1860*
BRCA2 K1872*
BRCA2 S1882*
BRCA2 Y1894*
BRCA2 L1952*
BRCA2 S1968*
BRCA2 Q1987*
BRCA2 Q1998*
BRCA2 Q2024*
BRCA2 E2028*
BRCA2 S2052*
BRCA2 S2095*
BRCA2 E2129*
BRCA2 Q2159*
BRCA2 G2281*
BRCA2 R2318*
BRCA2 Q2354*
BRCA2 L2362*
BRCA2 S2372*
BRCA2 L2375*
BRCA2 K2392*
BRCA2 R2401*
BRCA2 C2422*
BRCA2 L2428*

The following BRCA2 frameshift insertion mutants lack the HD and OB1 domains involved in SEM1 binding:
BRCA2 I27Mfs*6
BRCA2 P190Gfs*3
BRCA2 N255Kfs*21
BRCA2 T302Nfs*3
BRCA2 S309Ffs*6
BRCA2 A483Gfs*31
BRCA2 E532Rfs*3
BRCA2 H543Tfs*17
BRCA2 T582Kfs*3
BRCA2 I605Nfs*11
BRCA2 V726Sfs*25
BRCA2 H763Lfs*2
BRCA2 L769Hfs*21
BRCA2 L771Ifs*2
BRCA2 Y839Ifs*42
BRCA2 N863Kfs*18
BRCA2 L929Ffs*8
BRCA2 D946Rfs*13
BRCA2 Y949Lfs*10
BRCA2 N986Kfs*2
BRCA2 V1045Dfs*5
BRCA2 Q1089Sfs*10
BRCA2 N1287Kfs*2
BRCA2 T1359Yfs*2
BRCA2 C1365Mfs*3
BRCA2 L1390Ffs*13
BRCA2 V1532Sfs*2
BRCA2 V1532Efs*12
BRCA2 L1545Rfs*3
BRCA2 W1692Mfs*3
BRCA2 S1720Ffs*7
BRCA2 N1784Kfs*3
BRCA2 K1823Nfs*6
BRCA2 T2125Nfs*4

The following BRCA2 frameshift deletion mutants lack the HD and OB1 domains involved in SEM1 binding:
BRCA2 F62Lfs*18
BRCA2 R67Gfs*13
BRCA2 D252Vfs*24
BRCA2 E305Gfs*2
BRCA2 S313Lfs*11
BRCA2 V323*
BRCA2 R329Gfs*20
BRCA2 I332Ffs*17
BRCA2 Q407Rfs*23
BRCA2 C419Wfs*11
BRCA2 D420Tfs*10
BRCA2 K437Ifs*22
BRCA2 S450*
BRCA2 N460Kfs*6
BRCA2 V464Gfs*3
BRCA2 E470Kfs*15
BRCA2 K485Sfs*24
BRCA2 T515Ifs*10
BRCA2 M524Dfs*2
BRCA2 L557*
BRCA2 K585Nfs*3
BRCA2 I594Yfs*20
BRCA2 K601Rfs*14
BRCA2 I605Yfs*9
BRCA2 R645Efs*15
BRCA2 P655Qfs*5
BRCA2 L659*
BRCA2 P704Qfs*26
BRCA2 E718Kfs*12
BRCA2 E731Gfs*19
BRCA2 L759Ffs*3
BRCA2 M794Cfs*16
BRCA2 D806Mfs*4
BRCA2 N812Ifs*13
BRCA2 E816Kfs*9
BRCA2 L834Ffs*7
BRCA2 N863Ifs*11
BRCA2 S871Qfs*3
BRCA2 D885Mfs*9
BRCA2 D885Afs*10
BRCA2 T926Pfs*34
BRCA2 T933Rfs*2
BRCA2 G934*
BRCA2 A938Pfs*21
BRCA2 A938Efs*22
BRCA2 M965*
BRCA2 N986Ifs*5
BRCA2 F1005Lfs*38
BRCA2 K1026Ifs*10
BRCA2 T1040Lfs*3
BRCA2 D1054Efs*9
BRCA2 N1055Ifs*5
BRCA2 N1066Ifs*11
BRCA2 N1066Lfs*10
BRCA2 E1119Rfs*7
BRCA2 G1122Efs*28
BRCA2 V1144Cfs*6
BRCA2 T1154Pfs*14
BRCA2 F1182*
BRCA2 D1199Vfs*9
BRCA2 C1200*
BRCA2 V1214Wfs*14
BRCA2 S1230Lfs*9
BRCA2 I1258*
BRCA2 V1283Kfs*2
BRCA2 N1287Ifs*6
BRCA2 M1300*
BRCA2 E1353Vfs*5
BRCA2 H1362Tfs*12
BRCA2 I1364Mfs*3
BRCA2 K1406Nfs*3
BRCA2 F1421Kfs*4
BRCA2 D1451Ifs*12
BRCA2 L1491Kfs*12
BRCA2 K1517Ifs*23
BRCA2 V1532Lfs*11
BRCA2 N1544Tfs*24
BRCA2 S1650Vfs*20
BRCA2 K1691Nfs*15
BRCA2 L1776*
BRCA2 N1784Hfs*2
BRCA2 N1784Tfs*7
BRCA2 D1796Mfs*9
BRCA2 V1804Kfs*2
BRCA2 N1833Ifs*7
BRCA2 C1853Vfs*10
BRCA2 I1859Kfs*3
BRCA2 V1862*
BRCA2 D1868Vfs*5
BRCA2 M1890Tfs*15
BRCA2 L1908Rfs*2
BRCA2 H1918Cfs*20
BRCA2 I1962Mfs*42
BRCA2 L1965Ffs*39
BRCA2 F1978Lfs*26
BRCA2 S1982Rfs*22
BRCA2 D1990Cfs*12
BRCA2 G2044Afs*7
BRCA2 K2075*
BRCA2 G2078Ifs*2
BRCA2 L2092Pfs*7
BRCA2 N2135Kfs*3
BRCA2 S2148Yfs*2
BRCA2 Q2157Ifs*18
BRCA2 I2194Lfs*12
BRCA2 E2198Nfs*4
BRCA2 E2226Sfs*6
BRCA2 E2236Kfs*5
BRCA2 L2253Ffs*7
BRCA2 F2254Lfs*26
BRCA2 L2357Vfs*2
BRCA2 L2362Cfs*5
BRCA2 M2393*
BRCA2 K2404Sfs*7
BRCA2 N2452Mfs*15