ClinVar Genomic variation as it relates to human health

The copy number loss of 10q26.2q26.3 involves multiple protein-coding genes, including EBF3 (OMIM 607407). Deletions within 10q26.2q26.3 are associated with chromosome 10q26 deletion syndrome (OMIM 609625). The common clinical features include developmental delays (DD), distinctive facial dysmorphism, cardiac abnormalities, and urogenital anomalies (Lin 2016; Yatsenko 2009). A 500 kb minimal overlapping region of 10q26 deletion syndrome has been proposed which includes DOCK1, INSYN2 and NPS, which are not included in the current interval (Cherik 2021; Faria 2016). However, several reports have proposed other minimum critical regions for each phenotype, with the current interval being likely associated with craniofacial anomalies, DD, intellectual disability (ID) and possibly cardiac malformations (Ignatius 2020; Lacaria 2017; Lin 2016; Lopes 2017; Nishi 2021; Plaisancie 2014). Additionally, heterozygous sequence variants of EBF3 are associated with hypotonia, ataxia, and delayed development syndrome (HADDS; 617330), and there are multiple genes in this copy number loss that are associated with autosomal recessive disorders: NKX6-2 (OMIM 605955), TUBGCP2 (OMIM 617817), and ECHS1 (OMIM 602292). Even though copy number losses of this specific interval have not yet been associated with a clinical phenotype, there are no similar copy number losses of this region in the general populations of the Database of Genomic Variants. Thus, based on current medical literature and gene content, this copy number variant (CNV) is interpreted as pathogenic. Unique Rare Chromosome Disorders website has a booklet on 10q25 and 10q26 deletions which may be helpful for patient and family education (https://rarechromo.org/media/information/Chromosome%2010/10q25%20and% 2010q26%20deletions%20FTNW.pdf). References: Cherik et al., Eur J Med Genet. 2021 Jul 9;64(9):104287. PMID: 34252586. Faria et al., Am J Med Genet A. 2016 Feb;170A(2):403-9. PMID: 26566760. Ignatius et al., Neurol Genet. 2020 Jun 5;6(4):e444. PMID: 32637629. Lacaria et al., Am J Med Genet A. 2017 Jun;173(6):1611-1619. PMID: 28432728. Lin et al., Mol Med Rep. 2016 Dec;14(6):5134-5140. PMID: 27779662. Lopes et al., Front Genet. 2017 Oct 9;8:143. PMID: 29062322. Nishi et al., Am J Med Genet A. 2021 Oct;185(10):2913-2921. PMID: 34050706. Plaisancie et al., Eur J Med Genet. 2014 Jan;57(1):47-53. PMID: 24275544. Yatsenko et al., Clin Genet. 2009 Jul;76(1):54-62. PMID: 19558528.