Table 2. Clinical characteristics of patients with pathogenic/likely pathogenic variants in a hospital cohort.
| Gene | Case No. | HGVS cDNA | AA change | Cancer (Age) | Family history (age) | Reported/novel | Clinical relevance |
|---|---|---|---|---|---|---|---|
| BRCA1 | #7 #9 | c.3607C>T | p.R1203* | #7 BC (40) Tubal ca (67) #9 OC(43) |
#7 grandfather: laryngeal ca #9 no family history |
Reported (ClinVar, BX,BS,AURP), | Pathogenic |
| #15 | c.3637G>T | p.E1213* | BC (39) Ureter ca (60) | No family history | Reported (JCO)[37] | Pathogenic$ | |
| #22 | c.5332+1G>A | OC (42) BC(62) |
No family history | Reported (ClinVar, BX, AURP) | Pathogenic | ||
| #42 | c.2393_2393delC (2512delC) | p.V802* | OC (53) and BC (60) | Sister: OC (59), daughter: OC (35), father: esophageal ca (62) | Reported (ClinVar,BX) |
Pathogenic | |
| #57¶ | c.3472delG | p.E1158Kfs*2 | OC(55) | No family history | Novel | Likely pathogenic$ | |
| BRCA2 | #34 | c.1036delAA | p.N346fs_S356* | BC (26) | Maternal grandmother (40) and maternal aunt (70): BC | Novel | Likely pathogenic$ |
| #18 | c.7977-1G>T | IVS17-1G>T | BC (68) | Father (82), sister (36) and daughter (unknown): BC | Reported (ClinVar,BX) | Pathogenic(ClinVar/not reviewed(BX) | |
| #63¶ | c.7567_7568delCT | p.L2523EfsTer15 | BC (58) OC (61) | No family history | Reported (ClinVar,BX) |
Pathogenic | |
| RAD50 | #57¶ | c.1717delA | p.K574Nfs*24 | OC (55) | No family history | Novel | Likely Pathogenic$ |
| #50¶ | c.3553C>T | p.R1185* | BC (33) | Aunt (unknown): BC | Reported (ClinVar) | Pathogenic | |
| BRIP1 | #60¶ | c.2244C>G | p.Y748* | PPSC (56) | No family history | Novel | Likely Pathogenic$ |
Abbreviations: OC: ovarian cancer; BC: breast cancer; tubal ca: fallopian tube cancer; PPSC: primary peritoneal serous carcinoma. ClinVar: https://www.ncbi.nlm.nih.gov/clinvar/; BX (BRCAexchange): http://brcaexchange.org/; BS(BRCAshare): http://www.umd.be/BRCA1/ AURP: http://arup.utah.edu/database/BRCA/
JCO: BRCA1 and BRCA2 mutation frequency in women evaluated in a breast cancer risk evaluation clinic [37]
¶detected by the NGS panel.
$fulfilled 2015 ACMG criteria for likely pathogenic variant: 1PVS1 ((null variant framshift change or nonsense mutation) + 1 PM2 (absent from control)[32]