Genome-wide copy number analysis

Genome-wide copy number analysis may be considered for individuals in whom a chromosomal imbalance is suspected, especially when clinical features are complex, overlapping or not specific to a single gene disorder.

Testing may be appropriate for individuals with:

• Developmental delay or intellectual disability
• Autism spectrum disorder with additional clinical features
• Multiple congenital anomalies or dysmorphic features
• Suspected chromosomal imbalance
• Previous inconclusive genetic testing or relevant family history

Genome-wide copy number analysis can help identify an underlying chromosomal explanation for a patient’s clinical features. For patients and families, this may help shorten the diagnostic pathway and provide clearer information about the condition, prognosis and recurrence risk.

Testing may support:

• Confirmation or identification of a genetic diagnosis
• More targeted clinical management and surveillance
• Referral to appropriate specialists and support services
• Assessment of recurrence risk for family members
• Informed reproductive planning or further testing decisions

A genetic diagnosis can also prevent unnecessary investigations and provide a clearer basis for long-term care planning.

Genome-wide copy number analysis results are provided in a clinical diagnostic report. Depending on the test performed and the clinical indication, possible outcomes may include:

• Pathogenic or likely pathogenic CNV: a copy number variation is identified that explains, or is highly likely to explain, the patient’s clinical features and may help guide clinical management.
• Variant of uncertain significance (VUS): a CNV is identified, but current evidence is insufficient to classify it as disease-causing or benign. Interpretation may change as new scientific, clinical or family information becomes available.
• No reportable CNV detected: no clinically significant copy number change is identified by the assay. This result does not exclude a genetic condition due to inherent methodological limitations.
• Unexpected finding: in some cases, a CNV unrelated to the original indication may be identified and may have medical or reproductive relevance. Such findings are assessed and reported according to the test type, consent process, clinical context and laboratory policy.

The clinical impact of genome-wide copy number analysis depends on the CNV detected, the patient’s phenotype and current medical evidence.

A confirmed diagnosis may guide surveillance, treatment, referrals and multidisciplinary care, and may indicate whether relatives should be considered for targeted testing. Parental testing can help determine whether a CNV is inherited or de novo and support recurrence risk assessment, although germline mosaicism cannot always be fully excluded.

If no reportable CNV is identified, further testing may still be needed if clinical suspicion remains high, as some genetic alterations fall outside the scope of the test. VUS should be interpreted with caution and are generally not used in isolation for major medical or reproductive decisions. Reassessment may be appropriate as new clinical, family or scientific evidence becomes available.

We provide expert as an integral part of the genetic testing journey. Genetic counselling is a structured, educational, impartial and non-directive process that supports patients and families before and after testing.

Before testing, patients should receive clear information about the clinical aim, family history relevance, test methodology, benefits, limitations, possible outcomes, data privacy considerations and the potential role of family samples. This information should also explain how unexpected or additional findings may be handled, depending on the test type, consent process and laboratory policy.

After testing, counselling supports patients and physicians in interpreting the results in the context of the patient’s clinical features. This may include discussion of inheritance, recurrence risk, family testing, reproductive options, medical follow-up and whether further investigations may be recommended.

Availability of genetic counselling services may vary by country. Please for more information about access in your region.

• Hollenbeck D, Williams CL, Drazba K, et al. 2017. Clinical relevance of small copy-number variants in chromosomal microarray clinical testing. Genetics in Medicine. 19:377–385. PMID:
• Miller DT, Adam MP, Aradhya S, et al. 2010. Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. American Journal of Human Genetics. 86:749–764. PMID:
• Riggs ER, Andersen EF, Cherry AM, et al. 2020. Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of ACMG and ClinGen. Genetics in Medicine. 22:245–257. PMID:
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