Newborns gene panel
The list of genes for the conditions screened for in the Newborn Screening Pipeline is managed via Genomics England PanelApp. The Newborn Genomes Superpanel (1275) contains the list of genes and the corresponding conditions that will be screened for in the Generation Study. The superpanel is comprised of four different panels, these different panels are needed to account for different disease associations, modes of inheritance, and modes of pathogenicity per gene:
- Newborns main panel includes all genes.
- Newborns additional phenotype panel 1, 2 and 3 are component panels that include genes which have multiple phenotypes or multiple modes of inheritance.
Only genes that have been annotated as Green will be used in variant prioritisation. Genes can additionally have annotations and specific tags that determine how variants are prioritised in that gene (Figure 4).
Each gene is annotated with the mode of inheritance that will be screened for. The possible values of the mode of inheritance in the Newborn panel are listed in Table 1.
| Mode of Inheritance in Newborns’ Panel | Alternate definition |
|---|---|
MONOALLELIC |
Autosomal dominant |
BIALLELIC |
Autosomal recessive (simple recessive and compound recessive) |
X-LINKED |
X-linked, see entity mode of inheritance description for details on dominant/recessive |
Table 1. Modes of inheritances in Newborns’ Panel
Note
If the gene is considered for multiple modes of inheritance, separate gene entries are added in additional phenotype panels. The mode of inheritance annotation “BOTH” is not used in any Newborn panel.
The suitability of genes and conditions for use in the study is continually evaluated. If a gene needs to be removed from the study, it will be downgraded from “Green” to “Amber” or “Red” in the panels, and the pipeline will be updated accordingly. However, there may be a delay in which variants in these genes are prioritised despite their removal from the panel. These variants should not be reported. For more details, including current genes for which prioritised variants should not be reported, see Variant Review SOP.
- Each gene is annotated with the mode of pathogenicity. Genes that are annotated with
Loss-of-function variants DO NOT cause this phenotype(Figure 4) will not be considered for the LOF prioritisation component (see details below) and variants will only be prioritised via inclusion lists. - Genes with the tag
special_consideration(Figure 4) suggests that additional information needs to be considered during interpretation of variants prioritised in the gene. For a full list of special consideration categories, see Appendix A in the Variant Review SOP. - Genes with the tag
internal_inclusion_list_only(Figure 4) are those where only variants from the internal inclusion list will be prioritised (not ClinVar or CVA variants). For these genes the LOF algorithm may also be applied if annotated with a LOF mode of pathogenicity.
Figure 4: An example of a green gene which has a special_consideration tag, and an internal_inclusion_list_only tag. This gene is also annotated with mode of pathogenicity Loss-of-function variants DO NOT cause this phenotype, therefore LOF prioritisation would not be applied.