Table 1.
Characteristics of the Five Candidate Variants in 6q23–q26 for Familial Lung Cancer in Family A
| Gene | Genomic Positiona | Genomic Mutation | Exon | Protein Alteration |
Predicted Effect of Missense Mutation |
dbSNP137 | ESP MAFf | |||
|---|---|---|---|---|---|---|---|---|---|---|
| PolyPhen-2b | SIFTc | FATHMMd | GERP++e | |||||||
| PARK2 | chr6: 162,206,852 | c.823C>T | 7 | p.Arg275Trp | probably damaging (1.00) | deleterious (0.00) | potentially associated with cancer (−3.47) | 4.87 | rs34424986 | 0.002 |
| UTRN | chr6: 144,808,805 | c.3944A>C | 28 | p.Asn1315Thr | probably damaging (0.992) | deleterious (0.00) | not associated with cancer (1.78) | 3.95 | NA | NA |
| UTRN | chr6: 145,021,364 | c.7794G>C | 52 | p.Gln2598His | probably damaging (0.99) | deleterious (0.00) | not associated with cancer (1.58) | −2.12 | NA | NA |
| NOX3 | chr6: 155,776,042 | c.158G>T | 3 | p.Trp53Leu | probably damaging (0.996) | tolerated (1.00) | potentially associated with cancer (−3.48) | 5.91 | rs200865731 | NA |
| PACRG | chr6: 163,149,345 | c.78A>C | 2 | p.Gln26His | benign (0.19) | deleterious (0.01) | not associated with cancer (0.77) | −1.18 | rs80012280 | NA |
Abbreviations are as follows: ESP, NHLBI Exome Sequencing Project; and NA, not available.
Genomic positions are given according to the UCSC Genome Browser hg19 reference assembly.
PolyPhen-2 scores 0.85–1 are interpreted as probably damaging, scores 0.2–0.85 are possibly damaging, and scores 0–0.2 are benign.
SIFT scores range 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.
Predictions with FATHMM scores less than −0.75 indicate that the mutation is potentially associated with cancer; otherwise, the mutation is not associated with cancer.
An indication of evolutionary conservation is made if a given site shows a GERP++ score > 2.
MAFs are according to the NHLBI GO Exome Sequencing Project (ESP6500SI-V2 release) Exome Variant Server v.0.0.21 (August 2013).