Classify a genomic variant

Upload a classification framework and the evidence for a variant, and Anara walks through each criterion, states what the evidence supports, and returns a classification with reasoning traceable to your documents. Use it for a structured, auditable application of frameworks like ACMG/AMP.

Prompt

A clinical geneticist at a diagnostic laboratory classifies a CFTR variant for a patient with an atypical phenotype.

I need to classify this CFTR variant: c.1521_1523delCTT (p.Phe508del). I have uploaded: the ACMG/AMP variant classification guidelines (Richards et al. 2015), the CFTR2 program classification guidance, and the relevant population frequency data from gnomAD v3.

Apply the ACMG/AMP criteria to this variant using only the uploaded documents and the data I have provided. Walk through each criterion category:
- PVS1 (null variant)
- PS1-PS4 (strong pathogenic)
- PM1-PM6 (moderate pathogenic)
- PP1-PP5 (supporting pathogenic)
- BA1, BS1-BS4, BP1-BP7 (benign criteria)

For each criterion, state whether it applies, does not apply, or whether the evidence is insufficient to evaluate. Give the reason for each decision with reference to the specific guideline text. State the final classification and the combination of criteria that produced it.

What to add to your library

• Required: the classification framework as a PDF, such as ACMG/AMP criteria or disease-specific guidance.
• Required: the variant data: coordinates, transcript, protein change, and any functional, population frequency, or segregation data.
• Optional: published case reports or functional studies on this variant or the same codon.
• Optional: prior classifications of this or related variants from ClinVar or your institution.

What you get

• A criterion-by-criterion walk-through, each decision citing the guideline text.
• A clear status per criterion: met, not met, or insufficient evidence.
• The final classification and the combination of criteria that produced it, structured for institutional review.

Follow-ups

Find the evidence that would resolve uncertain criteria.

For the criteria you rated as insufficient evidence, tell me: what specific type of data would be needed to evaluate each criterion? What is the most practical source for each data type, and what change to the classification would each positive result produce?

Check whether reasoning from a nearby variant transfers.

The variant c.1521_1523delCTT is a deletion of phenylalanine at position 508. Search my library for any prior classification documents that address this position or nearby in-frame deletions in CFTR. Does any prior reasoning for an adjacent variant carry over to this one under the PS1 or PM5 criteria?

Tips

• Give the variant in HGVS notation plus a plain description of the change type. It reduces errors in the PVS1 evaluation.
• Anara does not access ClinVar or literature outside your library. If it is not uploaded, it is not in the assessment.
• Laboratory director review remains required when the classification drives a clinical action.