Mutational Signatures (v3.2 - March 2021)
SBS10c · GRCh37 · COSMIC v94
Mutational profile
Mutational profile using the conventional 96 mutation type classification. This classification is based on the six substitution subtypes: C>A, C>G, C>T, T>A, T>C, and T>G, as well as the nucleotides immediately 5’ and 3’ to the mutation.
Each of the substitutions is referred to by the pyrimidine of the mutated Watson—Crick base pair. Incorporating information on the bases immediately 5’ and 3’ to each mutated base generates 96 possible mutation types (6 types of substitution x 4 types of 5’ base x 4 types of 3’ base). Mutational signatures are displayed and reported based on the observed trinucleotide frequency of the genome, i.e., representing the relative proportions of mutations generated by each signature based on the actual trinucleotide frequencies of the corresponding reference genome.
Genome: GRCh37
Proposed aetiology
Defective POLD1 proofreading.
Comments
Strong lagging replication strand bias. Enriched in non-coding genome (intergenic and intronic) regions.
Acceptance criteria
Summary of the technical and experimental evidence available in the scientific literature regarding the validation of the mutational signature.
| Background | Identification study | First included in COSMIC | |
|---|---|---|---|
| Robinson et al. 2021 BioRxiv | v3.2 | ||
| Identification | NGS technique | Different variant callers | Multiple sequencing centres |
| WGS | No | No | |
| Technical validation | Validated in orthogonal techniques | Replicated in additional studies | Extended context enrichment |
| Yes | No | - | |
| Proposed aetiology | Mutational process | Support | |
| Defective POLD1 proofreading | Statistical association | ||
| Experimental validation | Experimental study | Species | |
| - | - | ||
Tissue distribution
Normal tissues from individuals with germline POLD1 exonuclease domain mutations
Associated signatures
Associated with ID1.
Differences between current and previous profiles
Genome: GRCh37