Table 2.
Pathogenic and Likely Pathogenic Variants Detected in Known Cancer Predisposition Genes
| Gene | Transcript | Variant (dbSNP) | Effect | Proband cancer | Cancer in Family | Heterozygous Cancer Risk1 |
|---|---|---|---|---|---|---|
| A- Whole Exome Sequencing | ||||||
| CHEK2 | NM_007194.3 | c.1100delC:p.Thr367Metfs (rs555607708) | Frameshift | UM, RCC, basal cell carcinoma | CM, breast | Breast |
| PALB2 | NM_024675.3 | c.3201+1G>C (rs587776423) | Splice site | UM, RCC | UM | Breast, Pancreatic |
| SMARCE1 | NM_003079.4 | c.373G>T, p.Glu125* (not reported) | Stopgain | UM, uterine | UM, Skin, | Meningioma |
| MLH1 | NM_001258271.1 | c.200G>A, p.Gly67Glu (rs63749939) | Non-synonymous | UM, breast (sebaceous adenocarcinoma) | UM, colon, skin, bladder, prostate, Hodgkins | Colon, ovarian, endometrial |
| B- BROCA Multi-Gene Panel | ||||||
| MSH6 | NM_000179.2 | c.C2731T: p.Arg911* (rs63751017) | Non-synonymous | UM, endometrial, BCC, SCC | Lynch syndrome in family | Colon, endometrial |
| BRCA1 | NM_007300.3 | c.C2603G: pSer868* (rs80356925) | Non-synonymous | UM, prostate | Breast × 3, stomach, mycosis fungoides, lymphoma, cervical, Skin, Liver | Breast, ovarian |
| ATM | NM_000051.3 | c.2251(−10)T>G (rs730881346) | Splice site | UM, lung | None | Breast, pancreatic |
| CHEK2 | NM_007194.3 | c.T470C:p.Ile157Thr (rs17879961) | Non-synonymous | UM | Pancreatic, breast × 2, colon | Breast |
| PALB2 | NM_024675.3 | c.49–1G>A (not reported) | Splice site | Breast, pancreatic | ||
| CTNNA1 | NM_001903 | c.1072_1075del AAAG: Arg360Valfs*8 (not reported) | Frameshift | UM | None | Gastric |
Pathogenic and likely pathogenic is based on ClinVar
Total of 156 unrelated proband with UM
1
Only the most commonly associated cancer types are listed.
BCC: Basel Cell Carcinoma; CM: Cutaneous Melanoma; RCC: Renal Cell Carcinoma; UM: Uveal Melanoma