Documentation / Getting Started / Understanding Results
Understanding Results
Results Organization
Results are organized by gene, not by individual variant. Each gene card shows a summary of the most clinically relevant variant in that gene. Expanding the card reveals all individual variants with their complete annotation data. This gene-centric view helps the geneticist focus on the biological context rather than individual base changes.
Variant Annotations
Each variant displays the following fields. Together, these provide the evidence a geneticist needs to assess clinical relevance.
ACMG Classification
Pathogenic, Likely Pathogenic, VUS, Likely Benign, or Benign. Determined by the Bayesian point system.
ACMG Criteria
Which specific criteria were triggered (e.g., PVS1, PM2, PP3_Strong) and their evidence strength levels.
Confidence Score
A continuous score reflecting the strength of classification evidence. Higher values indicate greater confidence in the classification.
Consequence
The predicted effect on the transcript: frameshift, missense, synonymous, splice donor, stop gained, and others.
Impact
Severity classification from Ensembl VEP: HIGH, MODERATE, LOW, or MODIFIER.
HGVS Notation
Standardized variant description at genomic (g.), coding (c.), and protein (p.) levels.
Genotype
Heterozygous (0/1), homozygous alternate (1/1), or hemizygous. Indicates the number of copies of the variant allele.
Population Frequency
gnomAD global allele frequency and population-specific maximum frequency. Lower frequency generally indicates higher clinical relevance.
ClinVar Significance
What ClinVar reports for this variant, with the review star level indicating assertion quality.
Computational Predictors
BayesDel score (used in classification) plus display predictors: SIFT, AlphaMissense, MetaSVM, DANN, PhyloP, GERP.
SpliceAI Scores
Four delta scores predicting splice impact: acceptor gain, acceptor loss, donor gain, donor loss.
Gene Constraint
pLI, LOEUF, and observed/expected loss-of-function ratio. Indicates how tolerant the gene is to damaging variation.
HPO Associations
Which clinical phenotypes are associated with this gene in the HPO database.
Phenotype Match Score
How well this gene matches the patient presentation (0-100), if HPO terms were provided.
Screening Tier
Tier 1 through 4 priority classification based on multi-dimensional scoring.
Literature Evidence
Relevant publications from the local PubMed database, ranked by clinical relevance.
What Each ACMG Classification Means
| Classification | Clinical Meaning | Action |
|---|---|---|
| Pathogenic | Variant causes disease. | Report to clinician. |
| Likely Pathogenic | Strong evidence variant causes disease (>90% certainty per ACMG). | Report to clinician. |
| VUS | Insufficient evidence to classify. | May require additional evidence gathering. |
| Likely Benign | Strong evidence variant does not cause disease. | Generally not reported. |
| Benign | Variant does not cause disease. | Not reported. |
Where to Start
The Screening Tier 1 list provides the highest-priority variants based on classification strength, phenotype correlation, population rarity, and gene constraint. Start there. If Tier 1 does not explain the clinical presentation, proceed to Tier 2 and consider additional evidence gathering for VUS candidates with strong phenotype matches.
For details on how screening tiers are assigned, see Screening Tier System. For classification methodology, see the full Methodology page.