Table 4 Classification of BRCA1/BRCA2 variants (unclassified variants) that were considered clinically not important in the Breast Cancer Information Core database
Unclassified variant classification method | Number of BRCA1 variants | Number of BRCA2 variants |
|---|---|---|
Allele frequency | ||
   High risk (LFUV) | 1 (1200H) | 15 (S326R, S384F, D596H, T598A, S976I, C1290Y, D1420Y, G1529R, H2116R, T2515I, A2717S, V2728I, S2835P, E2856A, T3013I) |
   Low risk (HFUV) | 2 (I379M, D693N) | 6 (N372H, N289H, L929S, N987I, N991D, T1414M) |
Polyphen | ||
   High risk (probable) | 0 | 3 (N987I, C1290Y, G1529R, H2116R) |
   Medium risk (possible) | 1 (I379M) | 8 (N289H, N372H, S384F, D596H, S976I, D1420Y, T2515I, E2856A) |
   Low risk (benign) | 2 (D693N, 1200H) | 9 (S326R, T598A, L929S, N991D, T1414M, A2717S, V2728I, S2835P, T3013I) |
Sequence conservation | ||
   High risk (high conservation) | 1 (I379M) | 4 (N289H, D596H, G1529R, E2856A) |
   Medium risk (moderate conservation) | 1 (Q1200H) | 10 (S326R, T598A, V2728I, S384F, S976I, N987I, C1290Y, D1420Y, H2116R, T2515I) |
   Low risk (low conservation) | 1 (D693N) | 7 (N372H, L929S, N991D, T1414M, A2717S, S2835P, T3013I) |
Grantham matrix score | ||
   High risk (>60) | 1 (Q1200H) | 17 (N289H, S326R, N372H, S384F, D596H, L929S, S976I; C1290Y, T1414M, D1420Y, G1529R, T2515I, A2717S, S2835P, N987I, E2856A, T3013I) |
   Low risk (≤ 60) | 2 (I379M, D693N) | 4 (T598A, N991D, H2116R, V2728I) |
Grantham matrix score/sequence conservation | ||
   High risk (deleterious) | 0 | 7 (N289H, D596H, L929S, N987I, 1420Y, G1529R, E2856A) |
   Medium risk (unclassified) | 2 (I379M, 1200H) | 7 (S326R, S384F, S976I, H2116R, T2515I, A2717S, T3013I) |
   Low risk (neutral) | 1 (D693N) | 7 (N372H, T598A, N991D, C1290Y, T1414M, V2728I, S2835P) |