Evidence profile

WGS rare disease proband profile

Public evidence profile for rare disease whole genome sequencing review in QuantBayes Studio.

Technical information

Profile UID: wgs_rare_disease_proband_v2
Version: 1.0
Visibility: Community
Domain: Clinical Genetics
Standard: SGA-QEM-1.0 v1.0
Maintainer: Swiss Genomics Association
Status: draft
Scope: Single proband WGS candidate variant review where evidence is assessed across genotype validity, population frequency, public clinical assertions, gene disease consistency, phenotype fit, control observations, and UniProt functional annotation.
Source file: Not specified
Checksum: Not set

How to read this table

Rule name, meaning, and flag describe how available data are interpreted before QuantBayes is run.

Each rule can return TRUE, FALSE, or NA. Under this QEM convention, only FALSE contributes supporting evidence.

Evidence shows the human interpretation. Matrix shows the binary value sent to QuantBayes.

Rules

Evidence interpretation rules

21 rules

Rule name	Meaning	Flag	Evidence	Matrix
Proband genotype invalid proband_genotype_invalid	The proband genotype is missing, invalid, failed, or cannot be interpreted reliably.	TRUE	No	0
Proband genotype invalid proband_genotype_invalid	The proband genotype is present, interpretable, and inspectable in the source data.	FALSE	Yes	1
Proband genotype invalid proband_genotype_invalid	Proband genotype evidence is unavailable or cannot be assessed.	NA	No	0
Population frequency common population_frequency_common	Population frequency is too high, exceeds the configured threshold, or is incompatible with a rare disease model.	TRUE	No	0
Population frequency common population_frequency_common	Population frequency evidence is available and remains below the configured rare disease threshold.	FALSE	Yes	1
Population frequency common population_frequency_common	Population frequency compatibility cannot be assessed.	NA	No	0
Population frequency unavailable population_frequency_unavailable	Population allele frequency evidence is missing, unavailable, or not traceable.	TRUE	No	0
Population frequency unavailable population_frequency_unavailable	Population allele frequency evidence is available from a traceable reference source.	FALSE	Yes	1
Population frequency unavailable population_frequency_unavailable	Population frequency availability is unknown or cannot be assessed.	NA	No	0
gnomAD flag present gnomad_flag_present	At least one gnomAD warning flag is present or the annotation has a flagged problem.	TRUE	No	0
gnomAD flag present gnomad_flag_present	No gnomAD warning flags are present and the population annotation is inspectable.	FALSE	Yes	1
gnomAD flag present gnomad_flag_present	gnomAD flag status is unavailable or cannot be assessed.	NA	No	0
ACMG benign evidence present acmg_benign_evidence_present	ACMG benign evidence is present, suggesting the variant may be harmless.	TRUE	No	0
ACMG benign evidence present acmg_benign_evidence_present	No ACMG benign evidence is present in the available annotation.	FALSE	Yes	1
ACMG benign evidence present acmg_benign_evidence_present	ACMG evidence is unavailable or cannot be assessed.	NA	No	0
ClinVar benign conflict clinvar_benign_conflict	ClinVar contains benign, likely benign, conflicting, or otherwise contradictory interpretation evidence.	TRUE	No	0
ClinVar benign conflict clinvar_benign_conflict	ClinVar evidence is available and no benign or conflicting interpretation is present.	FALSE	Yes	1
ClinVar benign conflict clinvar_benign_conflict	ClinVar evidence is unavailable or cannot be assessed.	NA	No	0
Gene disease validity weak genedisease_validity_weak	Gene disease validity is weak, missing, insufficient, or not traceable.	TRUE	No	0
Gene disease validity weak genedisease_validity_weak	Gene disease validity is present, traceable, and sufficient for the interpretation context.	FALSE	Yes	1
Gene disease validity weak genedisease_validity_weak	Gene disease validity evidence is unavailable or cannot be assessed.	NA	No	0
OMIM inconsistency omim_inconsistency	OMIM evidence is missing, contradictory, or inconsistent with the gene or inheritance context.	TRUE	No	0
OMIM inconsistency omim_inconsistency	OMIM evidence is present and compatible with the gene, disease, and inheritance context.	FALSE	Yes	1
OMIM inconsistency omim_inconsistency	OMIM evidence is unavailable or cannot be assessed.	NA	No	0
Loss of function mechanism inconsistent lof_mechanism_inconsistent	Loss of function mechanism evidence is inconsistent, unsupported, missing, or contradictory.	TRUE	No	0
Loss of function mechanism inconsistent lof_mechanism_inconsistent	Loss of function mechanism evidence is present and compatible with known gene biology.	FALSE	Yes	1
Loss of function mechanism inconsistent lof_mechanism_inconsistent	Loss of function mechanism evidence is unavailable, unmeasured, or not applicable.	NA	No	0
Phenotype mismatch phenotype_mismatch	Phenotype evidence is missing, insufficient, below threshold, or incompatible with the gene or disease model.	TRUE	No	0
Phenotype mismatch phenotype_mismatch	Phenotype evidence is available and sufficiently compatible with the gene or disease model.	FALSE	Yes	1
Phenotype mismatch phenotype_mismatch	Phenotype evidence is unavailable or cannot be assessed.	NA	No	0
Disease spectrum mismatch disease_spectrum_mismatch	Disease spectrum evidence is missing, insufficient, contradictory, or incompatible with the clinical presentation.	TRUE	No	0
Disease spectrum mismatch disease_spectrum_mismatch	Disease spectrum evidence is available and compatible with the clinical presentation.	FALSE	Yes	1
Disease spectrum mismatch disease_spectrum_mismatch	Disease spectrum evidence is unavailable or cannot be assessed.	NA	No	0
Present in controls present_in_controls	The variant is present in controls, control evidence conflicts with pathogenicity, or control review failed.	TRUE	No	0
Present in controls present_in_controls	Control evidence is available and the variant is absent from relevant unaffected controls.	FALSE	Yes	1
Present in controls present_in_controls	Control evidence is unavailable or cannot be assessed.	NA	No	0
No UniProt feature overlap flag_uniprot_no_feature_overlap	The variant lacks UniProt feature overlap, so functional annotation evidence is absent.	TRUE	No	0
No UniProt feature overlap flag_uniprot_no_feature_overlap	The variant overlaps a UniProt annotated feature and functional annotation evidence is available.	FALSE	Yes	1
No UniProt feature overlap flag_uniprot_no_feature_overlap	UniProt feature annotation is unavailable or cannot be assessed.	NA	No	0
No UniProt domain overlap flag_uniprot_no_domain_overlap	The variant lacks UniProt domain overlap, so domain evidence is absent.	TRUE	No	0
No UniProt domain overlap flag_uniprot_no_domain_overlap	The variant overlaps a UniProt domain-like region and domain evidence is available.	FALSE	Yes	1
No UniProt domain overlap flag_uniprot_no_domain_overlap	UniProt domain annotation is unavailable or cannot be assessed.	NA	No	0
No UniProt structural overlap flag_uniprot_no_structural_overlap	The variant lacks UniProt structural overlap, so structural evidence is absent.	TRUE	No	0
No UniProt structural overlap flag_uniprot_no_structural_overlap	The variant overlaps a UniProt structural element and structural evidence is available.	FALSE	Yes	1
No UniProt structural overlap flag_uniprot_no_structural_overlap	UniProt structural annotation is unavailable or cannot be assessed.	NA	No	0
No UniProt PTM overlap flag_uniprot_no_ptm_overlap	The variant lacks UniProt PTM overlap, so PTM evidence is absent.	TRUE	No	0
No UniProt PTM overlap flag_uniprot_no_ptm_overlap	The variant overlaps a UniProt post-translational modification region and PTM evidence is available.	FALSE	Yes	1
No UniProt PTM overlap flag_uniprot_no_ptm_overlap	UniProt PTM annotation is unavailable or cannot be assessed.	NA	No	0
No UniProt binding overlap flag_uniprot_no_binding_overlap	The variant lacks UniProt binding or active site overlap, so interaction evidence is absent.	TRUE	No	0
No UniProt binding overlap flag_uniprot_no_binding_overlap	The variant overlaps a UniProt binding or active site region and interaction evidence is available.	FALSE	Yes	1
No UniProt binding overlap flag_uniprot_no_binding_overlap	UniProt binding annotation is unavailable or cannot be assessed.	NA	No	0
No UniProt variant site overlap flag_uniprot_no_variant_site_overlap	The variant lacks UniProt variant or mutagenesis site overlap, so experimental evidence is absent.	TRUE	No	0
No UniProt variant site overlap flag_uniprot_no_variant_site_overlap	The variant overlaps a UniProt variant or mutagenesis site and experimental annotation evidence is available.	FALSE	Yes	1
No UniProt variant site overlap flag_uniprot_no_variant_site_overlap	UniProt experimental annotation is unavailable or cannot be assessed.	NA	No	0
Not loss of function flag_uniprot_not_lof	The variant is not predicted loss of function, so LoF mechanism evidence is absent.	TRUE	No	0
Not loss of function flag_uniprot_not_lof	The variant has a loss of function consequence and LoF mechanism evidence is available.	FALSE	Yes	1
Not loss of function flag_uniprot_not_lof	Variant consequence evidence is unavailable, unmeasured, or not applicable.	NA	No	0
NMD not predicted flag_uniprot_nmd_not_predicted	Nonsense-mediated decay is not predicted, so transcript loss of function evidence is absent.	TRUE	No	0
NMD not predicted flag_uniprot_nmd_not_predicted	Nonsense-mediated decay is predicted and transcript loss of function evidence is available.	FALSE	Yes	1
NMD not predicted flag_uniprot_nmd_not_predicted	NMD prediction evidence is unavailable, unmeasured, or not applicable.	NA	No	0
No UniProt feature truncation flag_uniprot_no_feature_truncation	The variant does not truncate a downstream UniProt annotated feature, so truncation evidence is absent.	TRUE	No	0
No UniProt feature truncation flag_uniprot_no_feature_truncation	The variant truncates a downstream UniProt annotated feature and truncation evidence is available.	FALSE	Yes	1
No UniProt feature truncation flag_uniprot_no_feature_truncation	UniProt truncation annotation is unavailable or cannot be assessed.	NA	No	0