Table 2.
Characteristics of patients with Deleterious or Likely Deleterious Variants
| Variant(s)a | Proband Cancer | Raceb and Family Historyc |
|---|---|---|
| TP53 c.451C>A, p.P151T (D) | Bilateral breast-31, ER-Her2+ | Race: W; M: Breast age>40, lymphoma; P: Breast age<40, colon ×2, brain |
|
TP53 c.733G>A, p.G245S (D) PALB2 c.94C>G, p.L32V (V) |
Breast-29, Unk | Race: U; Sib: Bilateral breast age<40; M: Breast age>40; P: colon |
| TP53 c.374C>T, p.T125M (LD) | Bilateral breast-30, DCIS | Race: A; M: None; P: Unknown |
| TP53 c.1000G>C, p.G334R (LD) | Breast-37, Unk; Breast-65,Unk |
Race: W/AJ; Sib: Colon; M: Breast age>40 ×3, leukemia, lymphoma, kidney, sarcoma, melanoma; P: colon |
|
CDKN2A c.104G>C, p.G35A (D) MSH6 c.3203G>A, p.R1068Q (V) |
Breast-38, Unk; Sarcoma-44 |
Race: W; M: Breast age>40, Melanoma; P: None |
| MSH2 del ex5 (LD) | Breast-39, ER+ Her2- | Race: W/AJ; M: None; P: thyroid, testicular |
|
MUTYH c.1187G>A, p.G396D (D); MUTYH c.281G>A, p.R94Q (LD) |
Colon-31; Breast-38, Unk; Breast-44, ER+Her2- | Race: W; M: Breast age<50, colon ×3, uterine; P: gallbladder |
| ATM c.8856delTC (D) | Breast-39, ER+ Her2+ | Race: W; M: None; P: pancreatic ×2, bladder, unknown gastrointestinal |
| ATM c.2282delCT (D) | Breast-39, DCIS | Race: A; M: Breast age>40 ×4; P: None |
| ATM c.6839delA (D) | Breast-34, DCIS | Race: W; M: Breast age<40 ×6, breast age>40 ×3, pancreatic, prostate, melanoma, brain; P: breast age>40 ×3, pancreatic |
| ATM c.7271T>G, p.V2424G (D) | Breast-29, ER+ Her2- | Race: A; M: Breast age>40; P: rectal, lung, brain ×2 |
| ATM 8774G>T, p.G2925V (LD) | Breast-31, ER+ Her2- | Race: W; M: Breast age>40 ×2, leukemia; P: None |
| ATM c.8155C>T, p.R2719C (LD) | Breast-38, ER+ Her2- | Race: A; M: Breast age>40; P: prostate |
| ATM c.8558C>G, p.T2853R (LD) | Breast-38, ER+ Her2- | Race: A; M: uterine; P: lung |
|
ATM c.8266A>T, p.K2756X (D) CHEK2 c.444+1G>A (D) |
Breast-32, Unk; Breast-40, ER+ Her2- |
Race: W; Sib: lung, prostate age 45; M: Breast age>40; P: prostate, melanoma, pancreatic, colon, breast age>40 |
| CHEK2 c.1100delC (D) | Breast-32, ER+ Her2- | Race: W; M: melanoma, breast age>40 ×2, colon ×3, uterine; P: Breast age<40×2 & age>40×2, brain |
| CHEK2 c.1100delC (D) | Breast-38, ER+ Her2- | Race: W; M: lung, thyroid; P: lung ×2 |
| CHEK2 c.1100delC (D) | Melanoma-30; Breast-34, Unk |
Race: W/AJ; M: Breast age<40 & age>40×3, prostate ×4; P: None |
| CHEK2 c.1555C>T, p.R519X (D) | Breast-37, ER+ | Race: W; M: Breast age>40, brain; P: None |
| CHEK2 c.444+1G>A (D) | Breast-32, ER-Her2+ | Race: W; P: Breast age>40, prostate; M: Breast age >40×2, leukemia, pancreatic, unknown gastrointestinal |
| CHEK2 c.470T>C, p.I157T (D) | Breast-36, Unk; Breast-49, ER+ Her2- |
Race: W; M: Breast age<40 & age>40 ×2, lung; P: breast age>40 |
| CHEK2 c.470T>C, p.I157T (D) | Breast-23, ER+ Her2+ | Race: W/AJ; M: Breast age>40, testicular, colon; P: none |
| CHEK2 c.349A>G, p.R117G (D) | Wilms-2; Breast-33, ER+ Her2+ | Race: W; M: None; P: prostate |
|
CHEK2 c.1283C>T, p.S428F (D) PMS2 c.944G>A, p.R315Q (V) |
Breast-38, ER+Her2+ | Race: W; M:adrenal, bladder, lung; P: None |
|
CHEK2 c.499G>A, p.G167R (LD) CHEK2 c.506T>C, p.F169Sd (LD) |
Breast-29, ER+ Her2- | Race: W/AJ; M: None; P: None; Sib (twin): breast age<40 |
| BARD1 c.1652C>G, p.S551X (D) | Breast-35, Unk; Breast-39, TNBC |
Race: W; M: None; P: Breast age>40 |
| BRIP1 c.2992delTT (D) | Breast-35, ER+; Bladder-44 |
Race: W/AJ; M: Breast age>40, colon, liver; P: Breast age>40, Lung |
| MRE11A c.1378G>T, p.E460X (D) | Breast-36, ER+ Her2+ | Race: W; M: Breast age<40, Breast age>40×2; P: lung |
| MRE11A c.1090C>T, p.R364X (D) | Breast-36, ER+ | Race: W; M: None; P: Breast age>40×3, uterine |
| RAD50 c.1252delTT (D) | Breast-31, ER+ Her2- | Race: A; M: Breast, Bone; P: None |
| NBN c.664T>C, p.F222L (LD) | Breast-37, Unk; Leukemia-39 |
Race: W; M: Breast age>40×2, P: melanoma, prostate, bladder, lymphoma |
a
D: deleterious variant, LD: likely deleterious variant, V: variant of unknown significance (VUS). The method of variant classification is described in the Methods section. Data supporting call for missense variants is provided in Supplementary Table 1.
b
W: White/Caucasian, A: African American, U: unknown; AJ: Ashkenazi Jewish descent
c
M: Cancers found on the maternal side, P: Cancers found on the paternal side; Sib: cancers found in siblings
d
The two CHEK2 mutations were shown to be in trans by analysis of 250 sequencing reads in IGV.