Gene Scoring
EAGLE Score
First presented in Schaaf et al. (2020), the EAGLE (Evaluation of Autism Gene Link Evidence) scoring system implements and expands on pre-existing frameworks (primarily the ClinGen (Clinical Genome Resource) framework) with the objective to evaluate evidence regarding the relevance of a gene with respect to ASD, rather than potentially with a broad range of neurodevelopmental phenotypes.
This protocol details the steps involved in curating the relationship between a gene and ASD, and subsequently assigning a classification. This curation process is not meant to be fully comprehensive, and should not be used to exclude a clinical genetic diagnosis. Additionally, as new evidence becomes available, re-evaluation of a gene may be necessary, incorporating new information that further clarifies the gene-ASD relationship. While the following protocol provides guidance on the curation process, professional judgement and expertise, where applicable, must be used when deciding on the strength of different pieces of evidence that support a gene-disease relationship.
12+ & Replicated over time Definitive
The role of this gene in ASD has been repeatedly demonstrated in both research and clinical settings, and has been upheld over time (at least 2 independent publications over 3 years’ time). No convincing evidence has emerged that contradicts the role of the gene in ASD.
12+ Strong
The role of this gene in ASD has been repeatedly demonstrated in both research and clinical settings, and has been upheld over time (at least 2 independent publications over 3 years’ time). No convincing evidence has emerged that contradicts the role of the gene in ASD.
7-11 Moderate
There is moderate evidence to support a causal role for this gene in ASD, including primarily case-level data, and potentially experimental data:
- At least 3 unrelated subjects harboring variants with sufficient evidence to support a role in ASD
- Moderate experimental data supporting the gene-ASD association (not necessary, but curators should document if it exists)
The role of this gene in ASD may not have been independently reported, but no convincing evidence has emerged that contradicts the role of the gene in ASD.
0.1-6 Limited
There is limited evidence to support a causal role for this gene in ASD, such as:
- Fewer than three observations of variants with sufficient evidence supporting a contribution of the gene to ASD OR
- Variants have been observed in ASD cases, but none have sufficient evidence for a strong contribution
- Experimental data may be limited or absent; as with previous categories, not necessary, but should be documented if it exists.
The role of this gene in ASD may not have been independently reported, but no convincing evidence has emerged that contradicts the role of the gene in ASD.