Table 1.
Whole-exome sequencing-based detection of high-quality exonic variants detected in ABCB1, ATR, BRCA1, BRCA2, CHEK1, H2AX, PARP1, and TP53 genes in PEO1 and PEO1-OR cell lines.
| Gene | Mutation | Gene Region | Amino Acid Change | Type of Mutation | Functional Impact | Computed Pathogenicity | CADD Score | Allele Fraction [% of Total Reads] |
Maximal Population Allele Frequency |
|
|---|---|---|---|---|---|---|---|---|---|---|
| PEO1 | PEO1-OR | |||||||||
| TP53 | c.731G > A | CDS | p.G244D | M | loss | pathogenic | 27 | 100% | 100% | 0% |
| BRCA1 | c.4837A > G | CDS | p.S1613G | M | normal | benign (!) | <10 | 100% | 100% | 49% (South Asian) |
| c.2082C > T | CDS | p.S694S | S | normal | benign | <10 | 100% | 100% | 49% (South Asian) |
|
| c.2311T > C | CDS | p.L771L | S | normal | benign | <10 | 100% | 100% | 49% (South Asian) |
|
| c.2612C > T | CDS | p.P871L | M | normal | benign (!) | 18 | 100% | 100% | 81% (African) |
|
| c.3113A > G | CDS | p.E1038G | M | normal | benign (!) | 14 | 100% | 100% | 49% (South Asian) |
|
| c.3548A > G | CDS | p.K1183R | M | normal | benign (!) | <10 | 100% | 100% | 49% (South Asian) |
|
| c.4308T > C | CDS | p.S1436S | S | normal | benign | <10 | 100% | 100% | 49% (South Asian) |
|
| c.-1074C > G | 5′ UTR | – | – | normal | benign | <10 | 100% | 100% | 82% (African) |
|
| c.-134T > C | 5′ UTR | – | – | normal | benign | <10 | 100% | 100% | 49% (South Asian) |
|
| BRCA2 | c.4965C > G | CDS | p.Y1655 * | STOP | loss | pathogenic | 33 | 100% | 100% | 0.008% (European) |
| c.4964A > T | CDS | p.Y1655F | M | normal | uncertain | <10 | 34% | 94% | 0% | |
| c.3807T > C | CDS | p.V1269V | S | normal | benign | <10 | 100% | 100% | 19% (African) |
|
| c.4563A > G | CDS | p.L1521L | S | normal | benign | <10 | 100% | 100% | 100% (Jewish) |
|
| c.6513G > C | CDS | p.V2171V | S | normal | benign | <10 | 100% | 100% | 100% (Jewish) |
|
| c.7397T > C | CDS | p.V2466A | M | normal | benign | <10 | 100% | 100% | 100% (Jewish) |
|
| c.* 105A > C | 3′ UTR | – | – | normal | benign | <10 | 100% | 100% | 23% (South Asian) |
|
| PARP1 | c.2285T > C | CDS | p.V762A | M | loss | benign (!) | 27 | 100% | 100% | 43% (East Asian) |
| c.243C > T | CDS | p.D81D | S | normal | benign | 12 | 100% | 100% | 43% (East Asian) |
|
| c.852T > C | CDS | p.A284A | S | normal | benign | <10 | 100% | 100% | 81% (East Asian) |
|
| c.-17G > C | 5′ UTR | – | – | normal | benign | 12 | 100% | 100% | 43% (East Asian) |
|
| ATR | c.632T > C | CDS | p.M211T | M | gain | benign (!) | 14 | 32% | 34% | 73% (African) |
| c.1776T > A | CDS | p.G592G | S | normal | benign | <10 | 31% | 31% | 79% (African) |
|
| c.1815T > C | CDS | p.D605D | S | normal | benign (!) | <10 | 32% | 31% | 44% (Jewish) |
|
| c.5208T > C | CDS | p.Y1736Y | S | normal | benign (!) | <10 | 29% | 30% | 45% (Jewish) |
|
| c.7875G > A | CDS | p.Q2625Q | S | normal | benign | <10 | 32% | 30% | 97% (African) |
|
| CHEK1 | c.1411A > G | CDS | p.I471V | M | gain | benign | 14 | 100% | 100% | 99.98% (East Asian) |
| c.* 28–3033C > G | 3′ UTR | – | – | normal | benign | <10 | 53% | 59% (LQ) | 42% (South Asian) |
|
| ABCB1 | c.210A > G | CDS | p.G70G | S | normal | benign | <10 | 100% | 100% | 100% (East Asian) |
| H2AX | c.-1420G > A | 5′ UTR | – | – | normal | benign | <10 | 53% | 35% (LQ) | 64% (East Asian) |
!—conflicting pathogenic criteria were computationally applied to a single variant (at least one pathogenic and one benign, as described in Section 3); 3′ UTR—3′ untranslated region; 5′ UTR—5′ untranslated region; CDS—protein-coding sequence; CADD score ranges from 1 to 99 (higher value responds to more deleterious cases, i.e., 10 indicates top 1% pathogenic variants, 20 indicates top 0.1% pathogenic variants); M—missense mutation; LQ—low-quality score for the variant allele call in one sample; S—synonymous mutation; STOP—stop-gain mutation; *—termiantion codon.