GEBRA™ Use Guide: Manual Curation – How to Build a Lasting Knowledge Layer From Your Interpretations

Product | 25. 12. 12

One of the most time-consuming steps in rare disease diagnostics is revisiting the same variant repeatedly.
Each time a new patient arrives, or when additional family information becomes available, previously interpreted variants must be reviewed again.
This repetitive work consumes valuable time—especially in situations where new evidence must be incorporated, such as:

When new case reports or functional studies are published
When updated family history or segregation data become available

To address these challenges, GEBRA™ enables Manual Curation that is applied in real time—without requiring reanalysis.

Why GEBRA™ Manual Curation? – Reduce Repetition, Improve Consistency

Manual Curation in GEBRA is more than a one-time annotation.
Once curated, your interpretation becomes part of a real-time knowledge layer, applied not only to the current sample but also automatically reused in all future analyses that include the same variant.

This provides several practical benefits:

Automatic application of updated interpretation without reanalysis
Consistent application of ACMG rules across your team
Elimination of redundant review in future cases
Effectively building your own variant knowledge base

Let’s take a look at how Manual Curation works in practice.

Where Do You Access Manual Curation?

From the variant card, click “See details” to open the detailed interpretation view.
In the example below, a DEPDC5 variant is used as a representative case.

Within the Classification section, you’ll find:

ACMG criteria
Evidence strength applied
Explanations supporting each rule

You can access Manual Curation by selecting the pencil icon in the upper-right corner of the section.

Curation Example 1 – Applying PP1 (Segregation Evidence)

If family testing shows that a DEPDC5 variant segregates with disease in five affected family members,
the PP1 (Segregation evidence) criterion can be applied.

In the curation interface:

Select PP1
Choose the evidence strength
Enter your justification in the Notes field

Once saved, this interpretation immediately applies to the current case and all future cases involving the same variant.

Curation Example 2 – Applying PS2 (De novo Evidence)

If trio analysis confirms the variant is de novo,
the PS2 criterion may be applied.

The process is the same:

Select PS2
Set the appropriate evidence strength
Record the justification in the Notes field

GEBRA stores this information at the variant level, ensuring that the same reasoning does not need to be repeated later.

How Are Curation Results Applied?

When you click Save:

The current interpretation is updated immediately
The curated criteria are automatically applied to all future analyses with the same variant
Your entire team benefits from consistent, unified interpretation standards

In other words, every Manual Curation entry becomes accumulated expert knowledge within your GEBRA platform.

Manual Curation + Knowledge Base = A More Powerful Interpretation Experience

In the previous guide, we introduced GEBRA’s Knowledge Base, a system designed to provide continuously growing clinical and analytical insights based on global case data and user-generated information.

Manual Curation acts as a key component of this system—specifically within the Curation DB, one of the three core Knowledge Base databases:

Curation DB – User-curated notes and ACMG evidence
Variant DB – Information on which variants appear in which patient samples
Reported DB – Records of which variants were included in clinical reports

Together, these resources allow GEBRA to function not as a platform where users “start from zero” each time,
but as a diagnostic knowledge system that continuously grows with its users.

If you’d like to revisit the Knowledge Base guide, you can explore it here:

👉 GEBRA™ Use Guide: Knowledge Base – Interpretations That Persist, Diagnoses That Compound