AutoCNV

AutoCNV performs clinical interpretation of constitutional copy number variants (CNVs), evaluating copy number loss and gain according to the 2019 ACMG/ClinGen technical standards.

Key Features:

• Standards compliance: Implements the 2019 American College of Medical Genetics and Genomics (ACMG) and ClinGen technical standards for CNV interpretation.
• Scoring criteria: Automatically scores CNVs using 18 criteria for copy number loss and 16 criteria for copy number gain.
• Semiautomatic processing: Provides semiautomatic handling of constitutional CNV evidence combining automated scoring with workflowed evaluation.
• Performance validation: Matched independent reviewer classifications 100% in a set of 72 CNVs and aligned 95% with ClinGen-verified classifications in example cases.
• Processing speed: Processes each CNV in under five milliseconds.
• Database-scale application: Applied to interpret CNVs from ClinVar and dbVar.

Scientific Applications:

• Clinical CNV interpretation: Interprets constitutional CNVs (copy number loss and gain) for clinical variant classification following ACMG/ClinGen guidelines.
• Benchmarking and validation: Validates CNV classifications against independent reviewer assessments and ClinGen-verified cases.
• Large-scale annotation: Enables high-throughput interpretation and annotation of CNVs from databases such as ClinVar and dbVar.
• Rapid genomic analyses: Supports fast decision-making in genomic studies through sub-5 ms per-CNV processing.

Methodology:

Automated scoring based on the ACMG/ClinGen 2019 criteria using 18 loss-specific and 16 gain-specific criteria in a semiautomatic workflow that outputs CNV classifications.