Related comments¶

The Related comments query retrieves comments in the local project based on a gene symbol, subject ID and, if desired, according to a user-defined threshold for the ACMG category 4 minimum allele frequency (Cat4minAF). The user may also designate a preferred VEP reference file (version). In addition, a relevance score (rscore) is calculated to indicate the degree of agreement between the phenotypes associated with the gene and those assigned to the subject (PN).

Example use case¶

The user wishes to review and evaluate comments made by other investigators (in their institution’s project) on variants in a gene of interest.

Description of the algorithm¶

This query creates a table of all variants with comments in the project for the selected gene. For the indicated subject, the phenotype terms “present” and “absent” in the subject are reported as being present or absent in that individual.

A PN relevance score (rscore) is calculated as follows:

First the subject’s assigned HPO code(s) (phenotypes) are mapped onto a phenotype-ontology tree structure (parent-child relationship between terms) generated from the HPO database.
Next, the score is weighted by a generelevance score, a similar HPO code term score calculated based on the gene’s associated HPO terms.

Higher scores indicate greater agreement between the gene-variant-associated phenotype terms and the subject’s associated phenotype terms.

Interpreting the output¶

Each row lists a variant and its related comments, including text entered by the user, mode of inheritance, user ID, whether the variant is starred or not, etc. These columns correspond to the entries in the CSA variant annotation page, shown below.

../_images/relatedComments_variant.png — Variant view in CSA¶

Note

Columns displayed depend on the formats of the annotation files

Column descriptions¶

Report output columns and descriptions¶
Group	Column	Description
Basic	alt
	chromo
	pn	Subject ID
	pos
	ref
gene	prevalence_button
	symbol	Based on HGNC when it exists, otherwise it is the Ensembl internal alias
MAX	AF	Maximum allele frequency reported from the following databases: EVS, EXAC, THGP3, GONL, and KYOTO
	consequence
	Score
other	allele	The alternative (reference) allele for the variant
	database_indicator
pheno	absent	Phenotype terms for the gene that are not associated with the subject
	present	Phenotype terms for the gene that are associated with the subject
report	section
	status
	type
variant	annotation_related
	review_status	User note on whether the variant is in process or to be reviewed at a later date
Other columns	amcg_variant_annotation_id
	approval_months
	approved_clinical_significance
	bam_confirmed	BAM file inspected to confirm the presence of the variant
	clinical_significance	Observed clinical significance as reported in HGMD, OMIM, or ACMG
	computation_data_indicator
	DIAG_ACMGcat	The ACMG category of the other variants (see DIAG_otherPos and DIAG_compPhases) that form compound heterozygosity with the variant
	disease	The associated disease or phenotype
	extDiseaseDescription
	extDiseaseId
	hgvscp	The HGVS coding/protein sequence name
	internal_comment	Comment internal to the project
	interpretation
	is_active	Yes (“1”) or no (“0”)
	last_approved_at
	mode_of_inheritance	Observed mode of inheritance
	onset
	parental_origin
	population_data_indicator
	query_context	Query filters used to identify variant
	reported_at
	reporting_category
	rscore	Relevance score based on the degree of agreement between the phenotype terms signed to the subject and gene input for this query. The score is weighted by the distance of the gene and subject terms (parent/child branch distance) in the HPO ontology tree. High scores indicate greater agreement between the phenotypes associated with the subject and the gene variant.
	sanger_status	Confirmed by Sanger sequence analysis or no
	severity
	study_id
	text	Text added by a user in the comments section for each variant
	transcript
	transcript_raw
	transcriptFeature
	type
	user_id	ID of the user
	VEP_Max_Impact	Summary of Variant Effect Predictor consequence: HIGH is truncating; MODERATE is missense and splice site; LOW is synonymous, UTR, and intron; LOWEST is intergenic, promoter, and other