Table 3.
Pathogenic and likely pathogenic variants identified by TruSight cancer sequencing panel in 20 patients with early-onset CRC.
| Patient ID | Clinical features (age at diagnosis/gender) | Ethnicity | Family history | Gene | Geno type | Mutation type | dbSNP ID | HGVSc | HGVSp | Database | Population frequency | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1000G | Esp6500 | ExAC | |||||||||||
| CRC2 | FAP; Sigmoid colon cancer (26/M) | Turk | A family member with FAP and CRC | APC | Het | Frameshift variant | NA | c.3613delA | p.Ser1205 AlafsTer60 | LOVD | NA | NA | NA |
| FANCI | Het | Frameshift variant | NA | c.3340delA | p.Thr1114 ProfsTer50 | Novel | NA | NA | NA | ||||
| CRC629 | Primary multiple metachronous cancer. Rectosigmoid colon cancer; BC; OC (47/F) | Russian | Mat. grandmother and mother: OC | BRCA1 | Het | Frameshift variant | rs39750724; rs80357906 | c.5329dupC (known as c.5382insC) | p.Gln1777 ProfsTer74 | LOVD, ClinVar | NA | NA | 0.02 |
| CRC622 | Cecum cancer (43/M) | Russian | Mother: ascending colon cancer; Mat.grandmother: gastric cancer | MLH1 | Het | Missense | rs267607706 | c.114C > G | p.Asn38Lys | LOVD, ClinVar | NA | NA | NA |
| CRC596 | PJS (20/M); Rectum Cancer (25) | German | Family members with CRC and diffuse polyposis | APC | Het | Stop-gain | rs1060503299 | c.3827C > G | p.Ser1276Ter | LOVD, ClinVar# | NA | NA | NA |
| CRC613 | FAP; Primary multiple synchronous cancer. Cancer splenic flexure; Rectum Cancer (39/F) | Father: Russian; Mother: Kazakh | A family member with FAP and CRC | APC | Het | Stop-gain | NA | c.4128T > G | p.Tyr1376Ter | Novel# | NA | NA | NA |
| CRC624 | Primary multiple synchronous cancer. Sigmoid colon cancer; Hepatic flexure of the colon cancer (46/M) | Russian | No family history | MLH1 | Het | In-frame deletion | rs121912962; rs587782285 | c.1852_1854 delAAG | p.Lys618del | LOVD, ClinVar# | NA | NA | NA |
| CRC344 | Primary multiple synchronous cancer. Ascending colon cancer; Rectum cancer (46/F) | German | No family history | BMPR1A | Het | Frameshift variant | NA | c.152delC | p.Ala51 AspfsTer9 | Novel | NA | NA | NA |
| CHEK2 | Het | Missense | rs17879961 | c.599T>C | p.Ile200Thr | ClinVar# | 0.1 | 0.16 | 0.41 | ||||
| CRC553 | Primary multiple metachronous cancer. Sigmoid colon cancer; Lung cancer (47/F) | Russian | No family history | FANCI | Het | Missense | NA | c.3623T>A | p.Leu1208Gln | Novel | NA | NA | NA |
| CRC371 | Hepatic flexure of the colon cancer (50/F) | Russian | No family history | BLM | Het | Frameshift variant | rs1555419829 | c.1316delT | p.Met439 ArgfsTer12 | ClinVar | NA | NA | NA |
| CRC382 | Rectum cancer (38/M) | Ukrainian | No family history | BRCA2 | Het | Frameshift variant | rs886040648 | c.6304_6305 delGT | p.Val2102 IlefsTer8 | ClinVar | NA | NA | NA |
| CRC442 | Rectosigmoid colon cancer (41/M) | Kazakh | No family history | MSH6 | Het | Frameshift variant | rs55740729 | c.4068_4071 dupGATT | p.Lys1358 AspfsTer2 | LOVD, ClinVar | NA | NA | 0.23 |
| CRC609 | Rectum cancer (40/M) | Kazakh | No family history | APC | Het | Frameshift variant | NA | c.907delA | p.Arg303 GlyfsTer2 | Novel | NA | NA | NA |
| NBN | Het | Frameshift variant | rs587776650 | c.657_661 delACAAA | p.Lys219 AsnfsTer16 | LOVD, ClinVar | NA | 1.45 | 0.02 | ||||
| ATM, C11ORF65 | Het | Frameshift variant | NA | c.6743dupA | p.Asp2249 GlyfsTer24 | Novel | NA | NA | NA | ||||
| CRC380 | Cancer splenic flexure (23/M) | Uigur | No family history | MUTYH | Het | Missense | rs34126013 | c.721C>T | p.Arg241Trp | LOVD, ClinVar | NA | NA | 0.01 |
| CRC137 | Sigmoid colon cancer (33/M) | Russian | No family history | AIP | Het | Missense | rs104894190 | c.911G>A | p.Arg304Gln | ClinVar, LOVD | NA | 0.07 | 0.14 |
| CRC545 | Rectum cancer (43/M) | Kazakh | No family history | BRCA2 | Het | Stop-gain | rs11571833 | c.9976A>T | p.Lys3326Ter | LOVD, ClinVar# | 0.44 | 0.65 | 0.7 |
| CRC616 | Sigmoid colon cancer (17/F) | Kazakh | NA | APC | Het | Stop-gain | NA | c.4128T>G | p.Tyr1376Ter | Novel# | NA | NA | NA |
| CRC628 | Rectum cancer (43/M) | Kazakh | No family history | DICER1 | Het | Stop-gain | NA | c.4991C>A | p.Ser1664Ter | Novel | NA | NA | NA |
| CRC581 | Rectum cancer (49/F) | Kazakh | No family history | BRCA1 | Het | Splice acceptor | rs878853285 | c.5341-2 delA | Unknown | ClinVar | NA | NA | NA |
| CRC558 | Cecum cancer (37/M) | Russian | No family history | FANCI | Het | Splice donor | rs1556861311 | c.2889+1G>A | Unknown | ClinVar | NA | NA | NA |
| CRC589 | Rectosigmoid colon cancer (46/M) | Tatar | No family history | BRCA2 | Het | Splice donor | rs886040935 | c.6937+1G>A | Unknown | ClinVar# | NA | NA | NA |
NA, not available; OC, ovarian cancer; BC, breast cancer; Mat.,maternal; Het, heterozygote; M, male; F, female;
#
, described in COSMIC.