Table 2. Germline variants and copy number variation (CNVs) identified and associated syndromes.
| Gene Variant | Classification | Associated Cancer or Syndrome (OMIM) | Patients with Variants (%) | dbSNP ID | 1000G MAF | ExAC MAF | NHLBI ESP MAF | HGMD |
|---|---|---|---|---|---|---|---|---|
| MUTYH | Likely Pathogenic | Colon cancer (604933) | 1 (1.15) | rs564930066 | 0.00040 | 0.00011 | 0 | NA |
|
NM_001128425 c.397G>C, p.D134H | ||||||||
| RET | Pathogenic | Multiple endocrine neoplasia type 2 (171400) | 1 (1.15) | rs146646971 | 0 | 0.00002 | 0.00046 | CM101836 (DM) |
|
NM_020630 c.1998G>T, p.K666N |
Familial medullary thyroid cancer (155240) | |||||||
| TSC2 | Pathogenic | Tuberous sclerosis complex (191100) | 1 (1.15) | NA | 0 | 0 | 0 | NA |
|
NM_000548 c.139-2A>G | ||||||||
| BRCA1 | Pathogenic | Hereditary breast-ovarian cancer syndrome (604370) | 1 (1.15) | rs80357711 | 0 | 0.00004 | 0 | CD961844 (DM) |
|
NM_007294 c.788-464delA, p.E1346fs*20 | ||||||||
| BRCA2 | Pathogenic | Hereditary breast-ovarian cancer syndrome (604370) | 1 (1.15) | NA | 0 | 0 | 0 | CD011121 (DM) |
|
NM_000059 c.4876_4877delAA, p.N1626fs*12 | ||||||||
| ERCC2 | Pathogenic | Xeroderma pigmentosum (278730) Trichothiodystrophy (601675) | 1 (1.15) | rs587778271 | 0 | 0.00009 | 0.00008 | CD013475 (DM) |
|
NM_000400 c.1703_1704delTT, p.F568fs*2 | ||||||||
| HRAS | NAa | Costello syndrome (218040) | 1 (1.15) | NA | 0 | 0 | 0 | NA |
| chr11:533276–534375 duplication |
aCNVs were not classified by Ingenuity Variant Analysis (IVA)
Abbreviations: OMIM, Online Mendelian Inheritance in Man; dbSNP, Single Nucleotide Polymorphism database; 1000G, 1000 Genome Project; MAF, Minor Allele Frequency; ExAC, Exome Aggregation Consortium; NHLBI-ESP, National Heart, Lung, and Blood Institute Exome Sequencing Project; HGMD, Human Gene Mutation Database; DM, Disease-causing mutation; NA, Not Available