Table 2. Higher Frequency of XPF (ERCC4) and XPC Mutations in Genetic Databases Compared With Phenotypic XP Observed in the United States.
| Complementation Group (Gene) | Mutation Associated With XP | Total No. of Alleles Sequenced | No. of Individuals | No. of Alleles | % of Alleles Reported in Database (q) | Estimated % of Homozygous Affected Individuals (q2)a | Total No. of Genetic Homozygotes Reported in Database | Total No. of Genetic Homozygotes Estimated in Databasea | rs No.b |
|---|---|---|---|---|---|---|---|---|---|
| gnomAD | |||||||||
| XPF (ERCC4) | p.P379S | 276 560 | 138 280 | 1122 | 0.41 | 1.65 × 10−5 | 4 | 2.28 | rs1799802 |
| XPF (ERCC4) | p.R799W | 277 034 | 138 517 | 124 | 0.04 | 2.00 × 10−7 | 0 | 0.03 | rs121913049 |
| XPC | p.P334H | 274 914 | 137 457 | 838 | 0.30 | 9.29 × 10−6 | 7 | 1.28 | rs74737358 |
| DCEG database (healthy controls) | |||||||||
| XPF (ERCC4) | p.P379S | 1996 | 998 | 10 | 0.50 | 2.51 × 10−5 | 0 | 0.03 | rs1799802 |
| XPF (ERCC4) | p.R799W | 1996 | 998 | 1 | 0.05 | 2.51 × 10−7 | 0 | 0 | rs121913049 |
| Inova Hospital Study database (healthy controls) | |||||||||
| XPF (ERCC4) | p.P379S | 1362 | 681 | 7c | 0.51 | 2.60 × 10−5 | 0 | 0.02 | rs1799802 |
| XPF (ERCC4) | p.R799W | 1362 | 681 | 1 | 0.07 | 4.90 × 10−7 | 0 | 0 | rs121913049 |
| XPC | p.P334H | 1362 | 681 | 8 | 0.59 | 3.48 × 10−5 | 0 | 0.02 | rs74737358 |
| US estimations | |||||||||
| XPF (ERCC4) | p.P379S | NA | 323 100 000d | NA | 0.41e | 1.65 × 10−5 | 3f | 5298g | rs1799802 |
| XPF (ERCC4) | p.R799W | NA | 323 100 000d | NA | 0.04e | 2.00 × 10−7 | 11f | 66g | rs121913049 |
| XPC | p.P334H | NA | 323 100 000d | NA | 0.30e | 9.29 × 10−6 | 1f | 3002g | rs74737358 |
| 65 XP mutationsh | NA | NA | NA | 1.13e | 2.81 × 10−5 | 300 (US only)f | 9007g | NA | |
Abbreviations: DCEG, Division of Cancer Epidemiology and Genetics; gnomAD, Genome Aggregation Database; NA, not available; XP, xeroderma pigmentosum.
a
Calculated using Hardy-Weinberg equation (see Methods section).
b
From the Single Nucleotide Polymorphism database (https://www.ncbi.nlm.nih.gov/projects/SNP/).
c
Calculated from the total number of alleles sequenced and the allele frequencies reported in Inova Hospital Study database.
d
In US populaton.
e
In gnomAD.
f
Phenotypic patients with XP reported in the world literature who are homozygous or heterozygous for indicated mutation.
g
Total number of genetic homozygous patients with XP predicted in United States based on gnomAD.
h
Mutations for XP in gnomAD (Table 1; eTable 2 in the Supplement).