Table 6 Pathogenic and likely pathogenic variants identified in BRCA1 and BRCA2
Sr No. | Patient ID | Age at diagnosis | Type | Gene | Variant Details | Exon | Consequence | Reported in multiple unrelated families in our cohort (Family #) | Previously Reported in Pakistani Patients (no. of individuals) | Novel Variants | Published literature |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Â | BRCA1 | Â | Â | Â | Â | Â | Â | Â | Â | Â | |
1 | 256 | 35 | U/L Breast Ca | BRCA1 | c.68_69del (p.Glu23Valfs*17) | 2 | Frameshift | also reported in one unrelated ovarian cancer patient | Yes (1,1,1) | – | PMID: 12181777, 31,528,241, (Risch et al., 2001) [21, 22, 41] |
2 | 22 | 36 | U/L Breast Ca | BRCA1 | c.1399_1453dup (p.Ala485Glufs*13) | 10 | Frameshift | – | Yes (1) | – | PMID:31528241 [22] |
3 | 36 | 25 | U/L Breast Ca | BRCA1 | c.1450G > T(p.Gly484*) | 10 | Non-sense | – | – | – | – |
4 | 51 | 34 | U/L Breast Ca | BRCA1 | c.685del (p.Ser229Leufs*5) | 10 | Frameshift | – | Yes (7) | – | PMID:31528241 [22] |
5 | 179 | 21 | U/L Breast Ca | BRCA1 | c.895_896del (p.Val299Argfs*4) | 10 | Frameshift | 179,191 | Yes (1) | – | PMID:31528241 [22] |
6 | 181 | 26 | U/L Breast Ca | BRCA1 | c.3607C > T (p.Arg1203*) | 10 | Non-sense | – | Yes (1) | – | PMID:31528241 [22] |
7 | 191 | 36 | U/L Breast Ca | BRCA1 | c.895_896del (p.Val299Argfs*4), | 10 | Frameshift | 179,191 | Yes (1) | – | PMID:31528241 [22] |
8 | 283 | 45 | Asymptomatic proband | BRCA1 | c.1583_1589del (p.Thr528Lysfs*2) | 10 | Frameshift | Â | Â | Â | Â |
9 | 194 | 37 | U/L Breast Ca | BRCA1 | c.3228_3229del (p.Gly1077Alafs*8) | 10 | Frameshift | – | – | – |  |
10 | 204 | 40 | U/L Breast Ca | BRCA1 | c.4065_4068del (p.Asn1355Lysfs*10) | 10 | Frameshift | – | Yes (4, 4, 1) | – | |
11 | 220 | 31 | U/L Breast Ca | BRCA1 | c.3169_3172del, p.Ser1057Leufs*4, | 10 | Frameshift | – | Yes (2) | – | PMID:31528241 [22] |
12 | 90 | – | Asymptomatic proband | BRCA1 | c.4485-1G > A | Intron 13 | Splice acceptor | 90, 145 | Yes (6) | – | PMID:31528241 [22] |
13 | 145 | 38, 47 | B/L Breast Ca | BRCA1 | c.4485-1G > A | Intron 13 | Splice acceptor | 90, 145 | Yes (6) | – | PMID:31528241 [22] |
14 | 223 | 32 | U/L Breast Ca | BRCA1 | c.4508C > A (p.Ser1503*) | 14 | Non-sense | 223,282 | Yes (3,1) | – | |
15 | 282 | 40 | U/L Breast Ca, Ovarian Ca | BRCA1 | c.4508C > A (p.Ser1503*) | 14 | Non-sense | 223,282 | – | – | – |
16 | 15 | 49 | U/L Breast Ca | BRCA1 | c.4821del, p.Ala1608Glnfs*25 | 15 | Frameshift | – | – | Yes | – |
17 | 82 | 30,43 | B/L Breast Ca | BRCA1 | c.5035del (p.Leu1679*) | 16 | Non-sense | 82, 251 | Yes (2) | – | – |
18 | 251 | 30 | B/L Breast Ca | BRCA1 | c.5035del (p.Leu1679*), | 16 | Non-sense | 82, 251 | – | – | – |
19 | 284 | 36 | U/L Breast Ca | BRCA1 | c.5074 + 1G > A | Intron 16 | Splice donor | 7284 |  | – | PMID:31528241 [22] |
20 | 7 | 27 | U/L Breast Ca | BRCA1 | c.5074 + 1G > A | Intron 16 | Splice donor | 7284 | Yes, (2) | _ | PMID:31528241 [22] |
21 | 31 | 28 | U/L Breast Ca | BRCA1 | c.5176delA (p.Arg1726Glufs*4), | 18 | Frameshift | – | – | – | – |
22 | 4 | 37 | U/L Breast Ca | BRCA1 | c.5278-1G > A | 19 | Splice acceptor | – | – | – | – |
23 | 235 | 31 | U/L Breast Ca | BRCA1, | c.5135G > A (p.Trp1712*), | 17 | Non-sense | – | – | – | – |
CHEK2 | Gain (Exons 3–4) | Gain of Ex. 3–4 | LGR | ||||||||
24 | 13 | 31 | U/L Breast Ca | BRCA1 | Deletion (Exons 1–11) | Deletion of Ex.1–11 | LGR | 13,278 | – | – | – |
25 | 278 | 37 | Asymptomatic proband | BRCA1 | Deletion (Exons 1–11) | Deletion of Ex.1–11 | LGR | 13,278 | – | – | – |
26 | 28 | 32 | U/L Breast Ca | BRCA1 | Deletion (Exon 1–6) | Deletion of Ex.1–6 | LGR | – |  | – | – |
27 | 109 | 34 | U/L Breast Ca | BRCA1 | Deletion (Exon 23) | Deletion of Ex.23 | LGR | – | – | – | – |
28 | 63 | 33 | U/L Breast Ca | BRCA1 | Gain (Exon 3–11) | Gain of Ex.3–11 | LGR | – | – | Yes | – |
29 | 6 | 30 | U/L Breast Ca | BRCA1 | Deletion of Exons 1–2 | Deletion of Ex.1–2 | LGR | – | Yes, (7) | – | PMID:31528241 [22] |
MSH6 | c.3261del (p.Phe1088Serfs*2) | 5 | Frameshift | Â | |||||||
| Â | BRCA2 | Â | Â | Â | Â | Â | Â | Â | Â | Â | |
30 | 105 | 62 | U/L Breast Ca | BRCA2 | Deletion (Exon 3) | Deletion of Ex.3 | LGR | – | – | – | – |
ATM | Deletion (Exon 43) | Deletion of Ex. 43 | LGR | ||||||||
31 | 45 | 53 | U/L Breast Ca | BRCA2 | c.426-2A > G | Intron 4 | Splice acceptor | – | Yes (1) | – | PMID:31528241 [22] |
32 | 257 | 35 | U/L Breast Ca | BRCA2 | c.859del (p.Met287Cysfs*5) | 10 | Frameshift | – | – | – | – |
33 | 119 | 55 | U/L Breast Ca | BRCA2 | c.3109C > T (p.Gln1037*) | 11 | Non-sense | – | Found in Asian patient (4) |  | PMID: 19241424 [43] |
34 | 1 | 52 | U/L Breast Ca | BRCA2 | c.4718del (p.Cys1573Leufs*6) | 11 | Frameshift | – | – | – | – |
35 | 34 | 41 | U/L Breast Ca | BRCA2 | c.6444dupT (p.Ile2149Tyrfs*2) | 11 | Frameshift | – | – | – | – |
36 | 185 | 36 | U/L Breast Ca | BRCA2 | c.4471_4474del (p.Leu1491Lysfs*12) | 11 | Frameshift | – | – | – | – |
37 | 76 | 48 | U/L Breast Ca | BRCA2 | c.7806-1G > C | Intron 16 | Splice acceptor | – | – | – | – |
38 | 200 | 40, 55 | B/L Breast Ca | BRCA2 | c.9380G > A (p.Trp3127*) | 25 | Non-sense | – | – | – | – |