HealthTech NHS Genomics England Rare Disease Data Platform

Genomics England Clinical Portal

NHS clinicians access genomic findings via the Genomics England Clinical Portal.

Data integration

• 1Genomics England API (Genomics England provides FHIR-based API for clinical interpretation -- variant data, phenotype data, clinical reports),
• 2VCF ingestion (Variant Call Format -- WGS variant data -- ingestion pipeline -- AWS S3 + GATK variant processing),
• 3phenotype data (HPO -- Human Phenotype Ontology -- patient phenotype data from NHS clinical teams),
• 4variant filtering (ClinVar, OMIM, gnomAD population frequency -- filter WGS variants for clinical significance),
• 5family data (trio analysis -- patient + parents -- de novo variant identification).

AWS

Genomics England uses AWS as primary cloud -- ClickMasters platform runs on same region (eu-west-2) as Genomics England data.

ACMG/AMP Variant Classification Engine

ACMG/AMP (American College of Medical Genetics / Association for Molecular Pathology) variant classification: 5-tier classification system (pathogenic, likely pathogenic, VUS, likely benign, benign).

Classification criteria

28 evidence criteria (PVS1, PS1-PS4, PM1-PM6, PP1-PP5, BA1, BS1-BS4, BP1-BP7).

Classification engine

• 1automated evidence gathering (ClinVar, gnomAD, OMIM, UniProt -- API queries for each variant),
• 2rule-based classification (ACMG/AMP rules applied to gathered evidence -- preliminary classification),
• 3clinical geneticist review (preliminary classification presented to geneticist -- review and override),
• 4classification audit log (every classification decision logged -- who classified, when, evidence used),
• 5variant curation database (classified variants stored -- future cases benefit from prior classification).

DCB0129

AI classification engine aids, never replaces clinical geneticist -- final classification always by qualified CLIA-certified clinical geneticist.

Genomic data GDPR

whole genome sequencing data is the most sensitive personal data category -- potentially identifiable even after pseudonymisation.

NHS GDPR additional safeguards for genomic data

• 1Genomics England data access committee (DAC) -- access to whole genome data requires DAC approval -- not available to ClickMasters platform without DAC,
• 2de-identified variant data (ClickMasters platform works with de-identified variant data -- no WGS reads, no direct identifiers),
• 3re-identification risk (WGS variant data can potentially re-identify individuals -- ICO guidance on genomic data),
• 4research ethics (NHS HRA IRAS approval required if genomic data used for research beyond direct care),
• 5patient consent (NHS Genomics England patients have consented to clinical care use -- research use requires separate consent).

ClickMasters genomics platform

clinical care use only -- no research use -- avoids IRAS and DAC requirements.

Rare disease clinical workflow integration

• 1MDT (Multi-Disciplinary Team) meeting support (variant report generated for MDT -- PDF summary of variant classification, disease association, treatment implications),
• 2OMIM disease annotation (Online Mendelian Inheritance in Man -- disease-gene associations -- every variant annotated with OMIM disease entries),
• 3treatment implications (NICE guidance and NHS specialised commissioning -- treatment pathways for rare diseases triggered by genomic findings),
• 4family cascade testing (if pathogenic variant found -- cascade testing for at-risk family members triggered),
• 5Genomics England recontact (Genomics England recontact policy -- if new evidence reclassifies VUS as pathogenic -- platform triggers recontact workflow).