Table 1.
Variants identified by sequencing with potential functional impact
| Gene | Change DNA/AA | G.dista | PhyloPb | SIFTc | MutationTasterd | PolyPhen2e | SNPs3Df | MutationAssessorg | TCGA | Samples |
|---|---|---|---|---|---|---|---|---|---|---|
|
POLE
NM_006231.2 |
c.1373A>T p.Tyr458Phe |
22 | 4.97 | 0.00 | 1 | 1.00 | −1.92 | 3.86 | 0 | III:2, IV:8, IV:9, IV:10, IV:13, IV:15, IV:17, IV:20, IV:21, V:4, V:5, V:8 |
|
BMPR1A
NM_004329.2 |
c.1379T>C p.Met460Thr |
81 | 3.35 | 0.00 | 1 | 0.49 | 0.14 | 1.81 | 1 h | V:7 |
|
EXO1
NM_003686.4 |
c.458C>T p.Ala153Val |
64 | 6.18 | 0.02 | 1 | 0.99 | −3.07 | 3.90 | 0 | IV:17 |
|
CHEK2
NM_007194.3 |
c.1100del p.Thr367Metfs*15 |
– | – | – | – | – | – | – | 3i | V:2 |
|
LAMB4
NM_007356.2 |
c.5265del p.Lys1755Asnfs*11 |
– | – | – | – | – | – | – | 1j | IV:6, V:2 |
The table shows gene name, variant at DNA and protein level, prediction of functional impact (Grantham’s physiochemical distance between pairs of amino acids, PhyloP basewise conservation score, SIFT, MutationTaster, PolyPhen2, SNPs3D, MutationAssessor; see footnotes for explanation of score values), number of samples with this variant in The Cancer Genome Atlas and the individuals in which the DNA variant was found. Individuals that were added after the initial exome sequencing (only Sanger sequenced) are shown in bold
aGrantham’s distance from 5 to 215
bSites predicted to be conserved are assigned positive scores, while sites predicted to be fast-evolving are assigned negative. Range −20 to +10 for the human genome
cScore values from 0 to 1. The amino acid substitution is predicted to be damaging if the score is ≤0.05, and tolerated if the score is >0.05
dPrediction of a disease-causing variant. P value close to 1 indicates a high confidence of the prediction
ePrediction of a change being damaging (>0.85), possibly damaging (0.15–0.85) or benign (<0.15) (HumVar)
fA positive score indicates a variant classified as non-deleterious, and a negative score indicates a deleterious variant. The larger the score, the more confident classification
gUses functional impact score to predict non-functional <1.938 or >1.938 functional impact
hFound in colorectal adenocarcinoma as a somatic change
iFound in one invasive breast carcinoma as a germline variant with loss of heterozygozity in the tumour. Also found in two cell lines
jFound as a somatic change in one stomach adenocarcinoma from 63 years old male. Copy number status for the gene was diploid