Table 1.
Sequence variants identified in theBRCA1gene
| Nucleotide Change | AA change | Number of patients | Clinical Relevance (BIC) | Variation class§ | Polyphen | SIFT | Align GVGD |
|---|---|---|---|---|---|---|---|
| Missense variations | |||||||
| 250 G > T |
C44F* |
2 |
Unknown |
5 |
+++ |
Not tolerated |
Class 65 |
| 543 C > G |
P142A* |
1 |
Not reported |
Not reported |
++ |
Not tolerated |
Class 0 |
| 585 C > A |
L156I |
1 |
Not reported |
3 |
+ |
Not tolerated |
Class 0 |
| 655A > G |
Y179C† |
2 |
Unknown |
1 |
+++ |
Not tolerated |
Class 45 |
| 1186A > G |
Q356R |
19 |
Unknown |
1 |
+++ |
Not tolerated |
Class 0 |
| 1575 T > C |
F486L† |
2 |
Unknown |
1 |
+ |
Tolerated |
Class 0 |
| 1767A > C |
N550H† |
2 |
Unknown |
1 |
++ |
Not tolerated |
Class 0 |
| 2196 G > A |
D693N |
11 |
No effect |
1 |
+ |
Not tolerated |
Class 0 |
| 2577A > G |
K820E |
1 |
Unknown |
1 |
+ |
Tolerated |
Class 0 |
| 2731 C > T |
P871L |
47 |
No effect |
1 |
+ |
Tolerated |
Class 0 |
| 3232A > G |
E1038G |
44 |
No effect |
1 |
+ |
Not tolerated |
Class 0 |
| 3238 G > A |
S1040N |
2 |
Unknown |
1 |
+ |
Tolerated |
Class 0 |
| 3646 T > A |
V1176I |
1 |
Unknown |
Not reported |
+ |
Tolerated |
Class 0 |
| 3667A > G |
K1183R |
43 |
No effect |
1 |
+ |
Tolerated |
Class 0 |
| 4755 G > A |
D1546N |
1 |
Unknown |
1 |
+ |
Tolerated |
Class 0 |
| 4773 T > C |
Y1552H |
1 |
Not reported |
3 |
++ |
Tolerated |
Class 0 |
| 4956A > G |
S1613G |
45 |
No effect |
1 |
+ |
Not tolerated |
Class 0 |
| 5075 G > A |
M1652I |
2 |
Unknown |
1 |
+ |
Tolerated |
Class 0 |
| Nonsense mutations | |||||||
| 5563 G > A |
W1815X |
2 |
Deleterious |
5 |
|
|
|
| Synonyms | |||||||
| 1964 T > C |
S615S |
2 |
Not reported |
Not reported |
|
|
|
| 2201 C > T |
S694S |
47 |
No effect |
1 |
|
|
|
| 2430 T > C |
L771L |
45 |
No effect |
1 |
|
|
|
| 4427 T > C |
S1436S |
44 |
Unknown |
1 |
|
|
|
| 5306 G > C |
L1729L |
1 |
Not reported |
Not reported |
|
|
|
| UTRs and Intronic variations | |||||||
| 66-67delTA |
5’-UTR |
29 |
Not reported |
Not reported |
|
|
|
| IVS2-91A > G |
|
1 |
Not reported |
Not reported |
|
|
|
| IVS5 + 45 T > A |
|
1 |
Not reported |
Not reported |
|
|
|
| IVS6 + 55 G > A |
|
2 |
Not reported |
3 |
|
|
|
| IVS7 + 15delTTC |
|
6 |
Not reported |
Not reported |
|
|
|
| IVS7-34 C > T |
|
17 |
No effect |
1 |
|
|
|
| IVS8-58delT |
|
10 |
No effect |
1 |
|
|
|
| IVS11 + 106 G > A |
|
64 |
Not reported |
Not reported |
|
|
|
| IVS13 + 117 G > A |
|
8 |
Unknown |
Not reported |
|
|
|
| IVS14-63 C > G |
|
25 |
Not reported |
Not reported |
|
|
|
| IVS18 + 66 G > A |
|
44 |
No effect |
1 |
|
|
|
| IVS19-26 G > A |
|
2 |
Not reported |
Not reported |
|
|
|
| IVS22 + 68 T > C |
|
1 |
Unknown |
3 |
|
|
|
| c.5711 + 36 C > G | 3’-UTR | 1 | Not reported | Not reported | |||
† Missense considered deleterious when associated.
*Missense considered deleterious.
Polyphen: +++ Variant predicted to be probably damaging, ++ Variant predicted to be possibly damaging, + Variant predicted to be benign.
UMD-BRCA1/2: 1 Variant considered neutral, 2 Variant considered likely-neutral, 3 Variant considered unclassified, 4 Variant considered likely-causal, 5 Variant considered causal.
§ in the UMD-BRCA1 database (http://www.umd.be/BRCA1/) (12) using classification system in five classes (13).