Table 2.
Sequence variants identified in theBRCA2gene
| Nucleotide Change | AA change | Number of patients | Clinical Relevance (BIC) | Variation class§ | Polyphen | SIFT | Align GVGD |
|---|---|---|---|---|---|---|---|
| Frameshift mutations | |||||||
| 5804_5808delTTAA |
I1859KfsX3 |
1 |
Deleterious |
5 |
|
|
|
| c.9485-1 G > A* |
|
1 |
Not reported |
Not reported |
|
|
|
| Missense variations | |||||||
| 353A > G |
Y42C |
1 |
Unknown |
1 |
+++ |
Tolerated |
Class 0 |
| 1093A > C |
N289H |
6 |
No effect |
1 |
+ |
Not tolerated |
Class 0 |
| 1342A > C |
N372H |
20 |
No effect |
1 |
+ |
Tolerated |
Class 0 |
| 3199A > G |
N991D |
2 |
Unknown |
1 |
++ |
Tolerated |
Class 0 |
| 5972 C > T |
T1915M |
2 |
Unknown |
1 |
++ |
Tolerated |
Class 0 |
| 6359 G > C |
G2044A |
1 |
Unknown |
3 |
+ |
Tolerated |
Class 0 |
| 6550 C > T |
R2108C |
1 |
Unknown |
3 |
+++ |
Tolerated |
Class 0 |
| 7625 C > T |
A2466V |
26 |
Unknown |
1 |
+ |
Not tolerated |
Class 0 |
| 9079 G > A |
A2951T |
1 |
No effect |
2 |
+ |
Not tolerated |
Class 55 |
| Nonsense mutations | |||||||
| 10204A > T |
K3326X |
1 |
No effect |
1 |
|
|
|
| Synonyms | |||||||
| 1593A > G |
S455S |
6 |
No effect |
1 |
|
|
|
| 2457 T > C |
H743H |
6 |
Unknown |
1 |
|
|
|
| 3624A > G |
K1132K |
16 |
No effect |
1 |
|
|
|
| 4035 T > C |
V1269V |
13 |
No effect |
1 |
|
|
|
| 4791A > G |
L1521L |
38 |
No effect |
2 |
|
|
|
| 5718 C > T |
S1830S |
1 |
Not reported |
Not reported |
|
|
|
| 6741 C > G |
V2171V |
38 |
Unknown |
1 |
|
|
|
| 7470A > G |
S2414S |
13 |
No effect |
1 |
|
|
|
| 10338 G > A |
R3370R |
1 |
Unknown |
1 |
|
|
|
| UTRs and Intronic variations | |||||||
| 203 G > A |
5’UTR |
16 |
No effect |
Not reported |
|
|
|
| IVS4 + 67A > C |
|
6 |
Unknown |
1 |
|
|
|
| IVS4 + 147 G > T |
|
4 |
Not reported |
Not reported |
|
|
|
| IVS6 + 14 C > T |
|
1 |
Unknown |
3 |
|
|
|
| IVS7 + 183 T > A |
|
21 |
Not reported |
1 |
|
|
|
| IVS7-9A > G |
|
1 |
Unknown |
Not reported |
|
|
|
| IVS8 + 56 C > T |
|
8 |
Unknown |
1 |
|
|
|
| IVS10-34 C > A |
|
1 |
Not reported |
3 |
|
|
|
| IVS10-51 G > T |
|
1 |
Not reported |
1 |
|
|
|
| IVS11 + 80delTTAA |
|
10 |
Unknown |
3 |
|
|
|
| IVS12-120 T > C |
|
37 |
Not reported |
3 |
|
|
|
| IVS13 + 133insATTATAAAA |
|
5 |
Not reported |
Not reported |
|
|
|
| IVS13 + 273 G > A |
|
2 |
Not reported |
Not reported |
|
|
|
| IVS14 + 53 C > T |
|
4 |
No effect |
Not reported |
|
|
|
| IVS16-14 T > C |
|
25 |
No effect |
1 |
|
|
|
| IVS21-66 T > C |
|
25 |
No effect |
1 |
|
|
|
| IVS22 + 53 C > G |
|
1 |
Not reported |
Not reported |
|
|
|
| IVS24-16 T > C |
|
1 |
Unknown |
1 |
|
|
|
| 10485 + 105A > C | 3’UTR | 15 | Not reported | Not reported | |||
*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).