# Copy Number Variation: Methods and Clinical Applications
## 3 Potential Biomedical Applications of CNV Detection
They demonstrated that their CNV pipeline can detect _EGFR_, _ERBB2_, and _MET_ amplification from ctDNA samples with high specificity and concordance with corresponding tissue-based whole-exome results. The concordance rate for _EGFR_, _ERBB2_, and _MET_ CNVs was 78%, 89.6%, and 92.4%, respectively [86]. The analysis of circulating nucleic acids may also be helpful in other diseases. Since cfDNA biomarkers are known to be important in many autoimmune and multifactorial diseases such as IBD [87], cfDNA could also be used for studying CNVs in such disorders. CNVs are also useful in the diagnostics of rare and common diseases or predispositions. This may be performed as prenatal testing through direct testing of the fetus or indirectly using maternal blood. Detection of CNVs is a common part of modern non-invasive prenatal testing (NIPT), most commonly based on low-coverage whole-genome sequencing analysis of cell-free fetal DNA (cffDNA) from maternal plasma [88]. This approach is useful for the detection of chromosomal aneuploidy and microdeletion syndromes, including DiGeorge, Prade-Willii/Angelman, 1p36, Cri-du-chat, and Wolf-Hirschhorn syndrome [52]. Apart from fetal CNVs, maternal ones can also be detected by this method, although current analyses generally do not interpret these findings. Maternal aberrations are potentially harmful to the fetus, so some authors suggest reporting these variants if clinically relevant. On the other hand, performing NIPT may lead to the incidental diagnosis of maternal diseases, such as previously unrecognized pathologies, late-onset diseases and predispositions arising from maternal germline CNVs, or malignancies and systemic autoimmune diseases presenting with somatic CNVs. Thus, these aspects of CNV detection also affect conventional perception of incidental and secondary findings arising via genetic testing, which are now extensively discussed [89]. [PERSON] et al. reported that 80% of genetic counselors recognized it would be beneficial to use NIPT for neoplasm screening, yet more than 90% affirmed that guidelines are necessary to prepare for such situations [90]. CNV detection may also find application in the evaluation of the microbiome balance, through the analysis of CNVs in metagenomes in different body parts. The human microbiome interacts with the host and plays an important role in many host biological processes [91]. Host genomic variations influence the composition of the microbiome, which in turn affects the health of the individual. While numerous studies have been focused on associations between the gut microbiome and specific alleles of the host genome, gene copy number also varies. It was shown, for instance, that duplication of the human _AMY1_ gene is associated with an increased number of oral _Porphyromonas_ in saliva, which is linked to periodontitis. Gut microbiota of these individuals had increased abundance of resistant starch-degrading microbes, produced higher levels of short-chain fatty acids, and drove higher adiposity when transferred to germ-free mice [92]. This case demonstrated that even seemingly harmless variants in the host genome could affect the health of an individual. Current knowledge suggests that it is important to analyze CNVs not only in human cells, but also in the microbiome. Taxonomic characterization of the human microbiota is often limited to the species level, however, each microbial species represents a large collection of strains that may contain considerably different sets or copy numbers of genes resulting in potentially distinct functional capacities. This intra-species variation is caused by deletion and duplication events, which were shown to be prevalent in the human gut environment, with some species exhibiting CNVs in >20% of their genes. This variability is especially prevalent in disease-associated genes involved in important functions, such as transport and signaling. A study by [PERSON] et al.