Extended Data Table 3 BRCA2 DBD subdomain specific multi-species amino acid residue conservation and comparison with MAVE functional results

From: Functional evaluation and clinical classification of BRCA2 variants

  1. *: Residues containing the Protospacer Protection Edit (PPE) sites were excluded.
  2. &: Missense changes with known splicing or potential splicing effects (SpliceAI > 0.2) excluded.
  3. +: P_Strong functional category was defined by the VarCall model.
  4. $: “Residues with P_Strong AA/residue (%)”: Of the 77 perfectly conserved residues in the helical subdomain, 45 residues contain at least one P-strong AA change.!: “Residues with P_Strong AA/total (%)”: Of all perfectly conserved residues with at least one P-strong AA change (n = 103), how many residues are located within each subdomain.
  5. #: “P-Strong AA/ total P_Strong AA (%)”: Of all 154 P-strong AA changes found in the helical subdomain, how many are perfectly conserved.
  6. DBD: DNA binding domain; MAVE: multiplex assays of variant effect; AA: amino acid.
  7. Perfectly conserved residues were defined as 100% residue sequence similarity across 10 species (pufferfish to homo sapiens).
  8. Highly conserved residues were defined as 80-90% residue sequence similarity across 10 species (pufferfish to homo sapiens).
  9. Poorly conserved residues were defined as ≤70% residue sequence similarity across 10 species (pufferfish to homo sapiens).
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