How-to guide for healthcare professionals: understanding genomic reports

Allele: Alternate forms of a gene at the same position on a chromosome. One allele is derived from paternal DNA and the other from maternal DNA.^1‒3

Amplification: An increase in the number of copies of a gene.¹

Base pair: The pair of complementary nucleotide bases that align together to form the ’rungs’ of the DNA double helix. Adenine pairs with thymine and guanine pairs with cytosine.¹

Bioinformatic analysis: Using computer technology to collate and interpret biological data; bioinformatic analysis of genomic data assesses differences in DNA and amino acid sequences.¹

Clinically actionable: Mutations for which there is clinical evidence to suggest potential to benefit from treatment with a specific therapy.^5,6

Clonality: Refers to how genetically similar the cells are within a tumour.³

Codon: A sequence of three nucleotides in DNA or RNA that encode for an amino acid.³ 

ctDNA (circulating tumour DNA): Small pieces of DNA that are released by a tumour into the blood stream.⁴

Deletion: When one or more nucleotide(s) are removed from part of the DNA sequence. The size of deletions can range from a single base pair to an entire piece of a chromosome.¹

DNA (deoxyribonucleic acid): The double helical molecule that carries the genetic information required for the development and functioning of a living organism.¹

Duplication: When there is one or more copy of a section of DNA. These can vary in length from a few base pairs to a whole chromosomal region.¹

ESCAT (ESMO Scale for Clinical Actionability of Molecular Targets): A six-tiered classification system developed by the European Society for Medical Oncology (ESMO), which defines clinical evidence-based criteria to prioritise genomic alterations as markers to select patients for targeted therapies.⁵

Frameshift mutation: Insertions or deletions that do not occur in multiples of three base pairs, thereby disrupting the codon reading frame (which is three base pairs long), leading to an altered protein sequence.¹

Gene fusions: When part of the DNA for one gene on one chromosome becomes attached to another gene on a different chromosome.⁴

Gene panel: The list of genes that were simultaneously sequenced for the particular type of cancer assessed by NGS.⁷

Germinal mutation: Variations in DNA that come from the egg/sperm cell and are present within all the cells of a person. These mutations are inherited and passed down from generation to generation.⁸

GLH (genomic laboratory hub): The network of laboratories responsible for coordinating genomic services across the NHS in England.⁹

Heterogeneity: A term referring to differences in genes and proteins, between individual cells. In this case, referring to tumour cells.⁴

Heterozygous: When an individual has two different alleles of the same gene.³

Homozygous: When an individual had two identical alleles of the same gene.³

Insertion: When one or more nucleotide(s) are added to a part of the DNA sequence. The size of insertions can range from a single base pair to an entire piece of a chromosome.¹

Locus: A specific position on a chromosome.³

NGS (next-generation sequencing): A method/technology for analysing DNA or RNA sequences in order to study genetic variation. It is a highspeed process that can sequence millions of fragments of DNA at the same time, with high accuracy.³

PCR (polymerase chain reaction): A laboratory technique for amplifying specific segments of DNA.¹

Point mutation: When only a single base pair is inserted, deleted, or changed in the DNA sequence. This can result in changes to the amino acid related to that specific codon, and thus the protein structure.¹

Recombinant: When genetic material is exchanged between or within chromosomes during meiosis.³

RNA (ribonucleic acid): A single stranded molecule that is similar to DNA, which is crucial for protein production.³

SNP (single nucleotide polymorphism): A common, small variation in a single base pair of DNA.^1,2

Somatic mutation: Variations in DNA that arise within individual cells of the body other than the sperm and egg and are therefore not inherited. They are usually localised to a particular organ or tissue.⁸

Transcriptome: The full set of RNA (transcripts) in a cell.²

Translocation: When parts of different chromosomes are switched. This happens when cells divide, and part of one chromosome breaks off and attaches to another (typically a swap).¹

VAF (variant allele frequency): A measure of the fraction of alleles that have the genomic variant, relative to the total number of alleles within a genomic locus.¹⁰

Variant/mutation: Any difference in the DNA sequence between two different genomes (or a reference genome).¹

References

1. National Human Genome Research. Talking glossary of genomic and genetic terms. Accessed November 2025. https://www.genome.gov/genetics-glossary 
2. National Library of Medicine. The NCBI handbook. 2nd Edition. 2013. Accessed November 2025. https://www.ncbi.nlm.nih.gov/books/NBK470040/
3. Genomics Education Programme. Genomics Glossary. Accessed November 2025. https:// www.genomicseducation.hee.nhs.uk/glossary/
4. National Cancer Institute Dictionary of Cancer Terms. Accessed November 2025. https://www.cancer.gov/publications/dictionaries/cancer-terms
5. Mateo J, Chakravarty D, Dienstmann R, et al. A framework to rank genomic alterations as targets for cancer precision medicine: the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT). Ann Oncol. 2018;29(9):1895–1902. 
6. Gornick MC, Ryan KA, Scherer AM, et al. Interpretations of the term “actionable” when discussing genetic test results: What you mean is not what I heard. J Genet Couns. 2018;28(2):334–342. 
7. NHS England National Genomics Education Programme. Gene panel sequencing. Accessed November 2025. https://www.genomicseducation.hee.nhs.uk/genotes/knowledge-hub/gene-panel-sequencing/
8. NHS England. National Genomics Education programme. Constitutional (germline) vs somatic (tumour) variants. Accessed November 2025. https://www.genomicseducation.hee.nhs.uk/genotes/knowledge-hub/constitutional-germline-vs-somatic-tumour-variants/
9. NHS England. Genomics Laboratory Hubs. Accessed November 2025. https://www.england.nhs.uk/genomics/genomic-laboratory-hubs/
10. Bielo LB, Trapani D, Repetto M, et al. Variant allele frequency: a decision-making tool in precision oncology? Trends Cancer. 2023;9(12):1058–1068.