Clusters of GVs detected in HAS1 gene exons and introns from patients with MM and WM
| . | Nucleotide changes . | Chromosomal location . | Type . | Effects on the protein . | Cluster* . |
|---|---|---|---|---|---|
| GVs clusters detected in MM patients | |||||
| Exon 3 | c>T | 56912163 | NCBI rs 1108411 | 1, 2, 3 | |
| Exon 3 | t>C | 56912056 | Germline origin | Val>Ala | 1 |
| Intron 4 | g>C | 56910770 | NCBI rs 11667974 | 1 | |
| Intron 4 | c>T | 56109315 | Germline origin | 2 | |
| Intron 4 | c>T | 56109217 | Germline origin | 2 | |
| Intron 4 | inst T | 56909764 | Germline origin | 2 | |
| Exon 3 | t>C | 56912051 | Germline origin | Cys>Arg | 3 |
| Intron 4 | g>C | 56910493 | NCBI rs 4802850 | 3 | |
| Intron 4 | c>A | 56910155 | NCBI rs 4802849 | 3 | |
| Intron 4 | c>G | 56910154 | NCBI rs 4802848 | 3 | |
| GVs clusters detected in WM patients | |||||
| Exon 3 | a>T | 56912068 | Tumor specific | Tyr>Phe | 1 |
| Intron 3 | a>G | 56911668 | Tumor specific | 2 | |
| Exon 4 | a>T | 56911346 | Hematopoietic origin | Met>Leu | 2 |
| Exon 4 | g>C | 56911348 | Hematopoietic origin | Arg>Pro | 2 |
| Intron 4 | g>t | 56910041 | Hematopoietic origin | 2 | |
| Intron 4 | t>C | 56909252 | Hematopoietic/germline origin | 3 | |
| Intron 4 | c>G | 56910154 | SNP-NCBI rs 4802848 | 3 | |
| Intron 4 | c>A | 56910155 | SNP-NCBI rs 4802849 | 3 | |
| Intron 4 | g>C | 56910493 | SNP-NCBI rs 4802850 | 3 | |
| Common motifs | |||||
| Intron 3 | t>A | 56911750 | SNP-NCBI rs 11669079 | ||
| Intron 3 | g>A | 56911831 | SNP-NCBI rs 11084109 | ||
| Intron 3 | g>A | 56911889 | SNP-NCBI rs 11084110 | ||
| Intron 4 | inst T | 56909604 | SNP-NCBI rs 11438660 | ||
| Intron 4 | inst (TTTA)s | 56909447 | Germline origin | ||
| Intron 4 | del (TTTA)s | 56909447 | Germline origin | ||
| Intron 4 | inst/del (T)s | 56909589 | Germline origin | ||
| Intron 4 | inst (Ts) | 56909762 | Germline origin | ||
| Intron 4 | c>T | 56909763 | SNP-NCBI rs 8104157 | ||
| Intron 4 | g>A | 56910711 | SNP-NCBI rs 7254072 | ||
| Intron 4 | t>G | 56910738 | SNP-NCBI rs 11667949 | ||
| . | Nucleotide changes . | Chromosomal location . | Type . | Effects on the protein . | Cluster* . |
|---|---|---|---|---|---|
| GVs clusters detected in MM patients | |||||
| Exon 3 | c>T | 56912163 | NCBI rs 1108411 | 1, 2, 3 | |
| Exon 3 | t>C | 56912056 | Germline origin | Val>Ala | 1 |
| Intron 4 | g>C | 56910770 | NCBI rs 11667974 | 1 | |
| Intron 4 | c>T | 56109315 | Germline origin | 2 | |
| Intron 4 | c>T | 56109217 | Germline origin | 2 | |
| Intron 4 | inst T | 56909764 | Germline origin | 2 | |
| Exon 3 | t>C | 56912051 | Germline origin | Cys>Arg | 3 |
| Intron 4 | g>C | 56910493 | NCBI rs 4802850 | 3 | |
| Intron 4 | c>A | 56910155 | NCBI rs 4802849 | 3 | |
| Intron 4 | c>G | 56910154 | NCBI rs 4802848 | 3 | |
| GVs clusters detected in WM patients | |||||
| Exon 3 | a>T | 56912068 | Tumor specific | Tyr>Phe | 1 |
| Intron 3 | a>G | 56911668 | Tumor specific | 2 | |
| Exon 4 | a>T | 56911346 | Hematopoietic origin | Met>Leu | 2 |
| Exon 4 | g>C | 56911348 | Hematopoietic origin | Arg>Pro | 2 |
| Intron 4 | g>t | 56910041 | Hematopoietic origin | 2 | |
| Intron 4 | t>C | 56909252 | Hematopoietic/germline origin | 3 | |
| Intron 4 | c>G | 56910154 | SNP-NCBI rs 4802848 | 3 | |
| Intron 4 | c>A | 56910155 | SNP-NCBI rs 4802849 | 3 | |
| Intron 4 | g>C | 56910493 | SNP-NCBI rs 4802850 | 3 | |
| Common motifs | |||||
| Intron 3 | t>A | 56911750 | SNP-NCBI rs 11669079 | ||
| Intron 3 | g>A | 56911831 | SNP-NCBI rs 11084109 | ||
| Intron 3 | g>A | 56911889 | SNP-NCBI rs 11084110 | ||
| Intron 4 | inst T | 56909604 | SNP-NCBI rs 11438660 | ||
| Intron 4 | inst (TTTA)s | 56909447 | Germline origin | ||
| Intron 4 | del (TTTA)s | 56909447 | Germline origin | ||
| Intron 4 | inst/del (T)s | 56909589 | Germline origin | ||
| Intron 4 | inst (Ts) | 56909762 | Germline origin | ||
| Intron 4 | c>T | 56909763 | SNP-NCBI rs 8104157 | ||
| Intron 4 | g>A | 56910711 | SNP-NCBI rs 7254072 | ||
| Intron 4 | t>G | 56910738 | SNP-NCBI rs 11667949 | ||
The first GV cluster of MM includes the common motif plus a recurrent hematopoietic origin missense mutation t>C (CH56912056) detected on exon 3 and NCBI-SNP rs 1667974. The second MM GV cluster comprises the common motif and 2 additional germline GVs, both on intron 4. The third MM GV cluster includes the common motif with an additional one germline origin missense t>C substitution (Cys>Arg) on exon 3 and 3 NCBI-SNPs on intron 4. All patients with MM were homozygous for mutated alleles of NCBI-SNPs included in the third GV cluster. WM GV cluster 1 includes the common motif plus a recurrent tumor-specific missense mutation a>T (Tyr>Phe, CH6912068) detected on exon 3. The second WM GV cluster includes the common motif and 4 additional hematopoietic origin GVs, missense mutations, a>T (CH56911346) and g>C (CH56911348) in exon 4, that lead to amino acid changes Met>Leu and Arg >Pro, respectively, one tumor specific in intron 4 (CH56910041), and one recurrent tumor-specific transition (CH5611668) in intron 3. The third WM GV cluster includes the common motif with an additional 4 GVs all detected in intron 4, 1 hematopoietic origin, and 3 NCBI-SNPs. Similar to patients with MM, all patients with WM were homozygous for mutated alleles of NCBI-SNPs included in any clusters.