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Table 2 Deleterious BRCA1/2 germline mutations in Pakistani breast/ovarian cancer families

From: Spectrum and prevalence of BRCA1/2 germline mutations in Pakistani breast cancer patients: results from a large comprehensive study

Family Exon BIC designation HGVS designation Mutation typeb Reported in databases (No. of entries)c
Nucleotide Codon Designation Nucleotide changea Effect on protein
BRCA1-small-range mutations
 432 2 185 23 185insA c.66dup p.(Glu23Argfs*18) FS BIC (32)d
 723 2 185 23 185delAG c.68_69del p.(Glu23Valfs*17) FS BIC (2036)d
 372 Intron 4 IVS4-2 - IVS4-2A>G c.135-2A>G Splice site SP BIC (1)
 254e 7 454 112 454delA c.335del p.(Asn112Ilefs*7) FS ClinVar (2)
 449 7 509 130 Y130X c.390C>G p.(Tyr130*) NS LOVD (3)
 296, 317, 340e, 511, 521, 626e, 747 11 804 229 804delT c.685del p.(Ser229Leufs*5) FS BIC (2)
 470e 11 903 262 Q262X c.784C>T p.(Gln262*) NS ClinVar (3)
 711 11 1014 299 1014delGT c.895_896del p.(Val299Argfs*4) FS BIC (2)
 669e 11 1127 336 1127delA c.1008del p.(Glu337Lysfs*4) FS Nod
 748 11 1307 396 1307delT c.1188del p.(Asp396Glufs*14) FS LOVD (1)
 241e 11 1309 397 1309delA c.1190del p.(Asp397Alafs*13) FS ClinVar (3)
 722 11 1518 485 1518_1572dup55 c.1399_1453dup p.(Ala485Glufs*13) FS No
 336e 11 1590 491 Q491X c.1471C>T p.(Gln491*) NS BIC (4)d
 N12 11 1898 593 1898delTATGGAA c.1779_1785del p.(Met594Serfs*3) FS LOVD (2)
 N28, 328e, 557e 11 1912 598 L598X c.1793T>G p.(Leu598*) NS BIC (1)d
 574e 11 2080 655 2080insA c.1961dup p.(Tyr655Valfs*18) FS BIC (13)d
 488e 11 2268 717 E717X c.2149G>T p.(Glu717*) NS ClinVar (2)
 236e, 283e, 489e, 493e, 593 11 2388 757 2388delG c.2269del p.(Val757Phefs*8) FS BIC (10)d
 363 11 2433 772 2433delGT c.2314_2315del p.(Val772Thrfs*4) FS LOVD (2)
 550h 11 2457 780 Q780X c.2338C>T p.(Gln780*) NS BIC (36)
 362, 469 11 2459 780 2459delGGAA c.2340_2343del p.(Glu781Valfs*10) FS LOVD (2)
 421e, 442, 510e, 542, 619e 11 2524 802 2524delTG c.2405_2406del p.(Val802Glufs*7) FS BIC (5)d
 N34 11 2657 846 2657delAAT-insG c.2538_2540delinsG p.(Met847Glyfs*4) FS LOVD (2)
 415e, 660e 11 2722 868 S868X c.2603C>G p.(Ser868*) NS BIC (11)d
 411e 11 3090 991 K991X c.2971A>T p.(Lys991*) NS ClinVar (2)
 247e 11 3100 994 3100delGT c.2981_2982del p.(Cys994*) FS ClinVar (5)
 299 11 3248 1043 3248delTATTAATGAA c.3129_3138del p.(Asn1043Lysfs*2) FS ClinVar (3)
 N13e, 399e 11 3458 1113 3458delTGA c.3339_3341del p.(Tyr1113*) FS ClinVar (2)
 610 11 3531 1138 G1138X c.3412G>T p.(Gly1138*) NS ClinVar (3)
 N25 11 3596 1159 3596delAAAG c.3477_3480del p.(Ile1159Metfs*50) FS BIC (3)
 279e, 445e 11 3717 1200 Q1200X c.3598C>T p.(Gln1200*) NS BIC (21)d
 382 11 3726 1203 R1203X c.3607C>T p.(Arg1203*) NS BIC (36)
 646 11 3819 1234 3819delGTAAA c.3700_3704del p.(Val1234Glnfs*8) FS BIC (61)
 210e, 211e, 313e, 316, 332e, 463, 520, 624, 652e, 653 11 3889 1257 3889delAG c.3770_3771del p.(Glu1257Glyfs*9) FS BIC (23)d
 N4e, 687, 724, 743 11 4184 1355 4184delTCAA c.4065_4068del p.(Asn1355Lysfs*10) FS BIC (144)d
 318e 12 4302 1395 Q1395X c.4183C>T p.(Gln1395*) NS BIC (28)d
 408e 13 4446 1443 R1443X c.4327C>T p.(Arg1443*) NS BIC (128)
 523e, 555, N18, 598e, 612, 621 Intron 14 IVS14-1 - IVS14-1G>A c.4485-1G>A Splice site SP BIC (2)d
 220e, 275e, 512e 15 4627 1503 S1503X c.4508C>A p.(Ser1503*) NS BIC (1)d
 609e 15 4784 1558 4784delG c.4665del p.(Arg1555Serfs*4) FS No
 611e 16 4981 1621 4981delA c.4862del p.(Asp1621Valfs*12) FS No
 249e, 658 17 5154 1679 5154delC c.5035del p.(Leu1679*) FS BIC (2)
 276e, 679 Intron 17 IVS17+1 - IVS17+1G>A c.5074+1G>A Splice site SP BIC (3)
 685 20 5358 1747 5358delC c.5239del p.(Gln1747Lysfs*18) FS LOVD (2)
 734 20 5385 1756 5385dupC c.5266dup p.(Gln1756Profs*74) FS LOVD (376)
 706 Intron 20 IVS20-1 - IVS20-1G>C c.5278-1G>C Splice site SP LOVD (5)d
 678 21 5429 1771 5429dupG c.5310dup p.(Pro1771Alafs*59) FS LOVD (1)
 278, 338e 22 5480 1787 5480delTG c.5361_5362del p.(Cys1787Trpfs*42) FS ClinVar (3)
 682 22 5496 1793 K1793X c.5377A>T p.(Lys1793*) NS ClinVar (1)
 248e Intron 23 IVS23-2 - IVS23-2A>T c.5468-2A>T Splice site SP ClinVar (1)
 260, 264, 329e, 377e, 389, 439, 481, 501, 522 24 5622 1835 R1835X c.5503C>T p.(Arg1835*) NS BIC (74)d
BRCA1-large genomic rearrangementse
 229, 291, 314, 379, 406, 498, 549 1-2 - - del exon 1-2 g.41271967_41308900delf   LGR (42)g
 261, 719 21-24 - - del exon 21-24 g.41172653_41205744delf   LGR No
BRCA2-small-range mutations
 497, 700 3 320 31 W31X c.92G>A p.(Trp31*) NS ClinVar (4)
 N26 Intron 4 IVS4-2 - IVS4-2A>G c.426-2A>G Splice site SP ClinVar (4)
 545 9 993 255 993delCACAA c.765_769del p.(Asn255Lysfs*19) FS No
 330 10 1528 434 1528delAAAA c.1300_1303del p.(Lys434Glufs*25) FS ClinVar (2)
 602 11 3048 941 3048delA c.2820del p.(Val941Cysfs*19) FS No
 206 11 3063 945 3063delA c.2835del p.(Asp946Ilefs*14) FS ClinVar (2)
 505 11 4088 1287 4088delA c.3860del p.(Asn1287Ilefs*6) FS BIC (2)
 222, 407h, 525, 540h 11 5450 1741 5450delGTAA c.5222_5225del p.(Ser1741Thrfs*35) FS BIC (1)
 627, 684 11 5910 1894 Y1894X c.5682C>A p.(Tyr1894*) NS BIC (3)
 295e 11 5950 1908 5950delCT c.5722_5723del p.(Leu1908Argfs*2) FS BIC (43)d
 447 11 6696 2156 6696delTC c.6468_6469del p.(Gln2157Ilefs*18) FS BIC (24)d
 548h 11 7044 2274 7044delAAGAG c.6816_6820del p.(Gly2274Alafs*17) FS ClinVar (6)
 579 15 7803 2526 7803delA c.7575del p.(Ala2526Glnfs*2) FS LOVD (2)
 492 Intron 17 IVS17+2 - IVS17+2C>A c.7976+2C>A Splice site SP ClinVar (1)
 713 20 8773 2849 8773delAA c.8545_8546del p.(Lys2849Glyfs*19) FS No
 702 20 8779 2860 8779_8798dup20 c.8551_8570dup p.(Lys2860Asnfs*10) FS No
 207h 21 8897 2890 8897insT c.8669dup p.(Thr2891Asnfs*16) FS ClinVar (1)
 538 Intron 21 IVS21+4 - IVS21+4A>G c.8754+4A>G Splice site SP BIC (7)
  1. aNumbering starts at the first A of the first coding ATG (located in exon 2) of NCBI GenBank accession number U14680 (BRCA1) and U43746 (BRCA2)
  2. bFS frameshift mutation, LGR large genomic rearrangement, MS missense mutation, NS nonsense mutation, SP splice-site mutation
  3. cBIC Breast Cancer Information Core database (https://research.nhgri.nih.gov/projects/bic/), LOVD Leiden Open Variation Database (http://databases.lovd.nl/shared/genes/BRCA2); ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/), date last accessed June 26, 2018
  4. dPreviously reported in Pakistani breast/ovarian cancer cases [9, 10]
  5. eFamilies and mutation description have been previously reported [11, 18]
  6. fGenomic locale for chromosome 17, from the UCSC genome browser, Feb 2009 assembly
  7. gNot available in databases; reported in various studies [1, 11]
  8. hFamilies with male breast cancer