Table 3.
Truncating mutations and nonsynonymous variants of PALB2 discovered in the present study
| Location | Nucleotide change |
Protein change | rs# (SNP132) | Variant type | Computational prediction | Minor allele frequency (MAF) | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SIFT | PolyPhen | PMUT | PANTHER | Align GVGD |
Re-score |
BRCA1/2 mutation positive cases (n = 19) |
BRCA1/2 mutation negative cases (n = 51) |
BRCA1/2 mutation unknown cases (n = 209) |
All cases (n = 279) |
Controls (n = 262) |
|||||
| exon2 | c.53A>G | p.Lys18Arg | - | nonsynonymous | tolerated (0.21) |
benign (1.252) |
neutral (0.046) |
neutral (−1.770) | C0 | benign (0) | 0.000 | 0.000 | 0.005 | 0.004 | - |
| exon4 | c.400G>A | p.Asp134Asn | - | nonsynonymous | tolerated (0.41) |
benign (0.979) |
neutral (0.154) |
neutral (−1.352) | C0 | benign (0) | 0.000 | 0.000 | 0.002 | 0.002 | - |
| exon4 | c.629C>T | p.Pro210Leu | rs57605939 | nonsynonymous | tolerated (0.44) |
benign (1.139) |
pathological (0.708) |
neutral (−0.666) | C0 | possibly benign (1) |
0.079 | 0.029 | 0.060 | 0.056 | - |
| exon4 | c.721A>G | p.Asn241Asp | rs113217267 | nonsynonymous | tolerated (0.62) |
benign (0.114) |
neutral (0.032) |
neutral (−0.597) | C0 | benign (0) | 0.000 | 0.030 | 0.014 | 0.016 | 0.004 |
| exon4 | c.758dupT | p.Ser254Ilefs*3 | - | frameshift- duplication |
truncating | truncating | truncating | truncating | truncating | truncating | 0.000 | 0.000 | 0.002 | 0.002 | 0.000 |
| exon4 | c.925A>G | p.Ile309Val | rs3809683 | nonsynonymous | tolerated (0.30) |
benign (0.097) |
neutral (0.045) |
neutral (−0.266) | C0 | benign (0) | 0.056 | 0.010 | 0.012 | 0.015 | 0.035 |
| exon4 | c.1010T>C | p.Leu337Ser | rs45494092 | nonsynonymous | tolerated (0.73) |
possibly damaging (1.691) |
pathological (0.734) |
neutral (−2.282) | C0 | possibly benign (1.5) |
0.000 | 0.010 | 0.005 | 0.005 | 0.004 |
| exon4 | c.1479delC | p.Thr494Leufs*67 | - | frameshift- deletion |
truncating | truncating | truncating | truncating | truncating | truncating | 0.000 | 0.000 | 0.002 | 0.002 | 0.000 |
| exon4 | c.1676A>G | p.Gln559Arg | rs152451 | nonsynonymous | tolerated (0.56) |
benign (0.175) |
neutral (0.070) |
neutral (−0.476) | C0 | benign (0) | 0.316 | 0.163 | 0.189 | 0.193 | 0.215 |
| exon5 | c.2014G>C | p.Glu672Gln | rs45532440 | nonsynonymous | tolerated (0.44) |
benign (1.348) |
neutral (0.107) |
neutral (−2.154) | C0 | benign (0) | 0.000 | 0.000 | 0.007 | 0.005 | - |
| exon7 | c.2590C>T | p.Pro864Ser | rs45568339 | nonsynonymous | tolerated (0.46) |
probably damaging (2.274) |
pathological (0.819) |
neutral (−1.5704) | C0 | possibly benign (2) |
0.000 | 0.020 | 0.002 | 0.005 | - |
| exon9 | c.2851T>C | p.Ser951Pro | - | nonsynonymous | tolerated (0.37) |
benign (0.044) |
pathological (0.652) |
neutral (−1.955) | C0 | possibly benign (1) |
0.000 | 0.010 | 0.000 | 0.002 | 0.002 |
| exon9 | c.2993G>A | p.Gly998Glu | rs45551636 | nonsynonymous | affect (0.01) | probably damaging (2.172) |
pathological (0.840) |
deleterious (− 4.581) |
C65 | deleterious (5) |
0.000 | 0.000 | 0.007 | 0.005 | 0.004 |
| exon10 | c.3048delT | p.Phe1016Leufs*17 | - | frameshift- deletion |
truncating | truncating | truncating | truncating | truncating | truncating | 0.000 | 0.000 | 0.002 | 0.002 | 0.000 |
| exon10 | c.3056T>C | p.Val1019Ala | - | nonsynonymous | affect (0.01) | possibly damaging (1.583) |
pathological (0.577) |
deleterious (− 3.190) |
C25 | possibly deleterious (4) |
0.000 | 0.000 | 0.002 | 0.002 | 0.000 |
Three truncating mutations, p.Ser254Ilefs*3, p.Thr494Leufs*67, and p.Phe1016Leufs*17 identified in this study are shown in bold.