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Table 4 Classification of BRCA1/BRCA2 variants (unclassified variants) that were considered clinically not important in the Breast Cancer Information Core database

From: Evaluation of unclassified variants in the breast cancer susceptibility genes BRCA1 and BRCA2using five methods: results from a population-based study of young breast cancer patients

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)
  1. LFUV, low-frequency unclassified variants; HFUV, high-frequency unclassified variants.