Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV002472553 | SCV002772421 | pathogenic | not provided | 2021-08-25 | criteria provided, single submitter | clinical testing | The copy number loss of 15q25.2 involves two protein-coding genes, GOLGA6L10 and RPS17 (OMIM 180472), and is expected to cause phenotypic and/or behavioral abnormalities. GOLGA6L10 is not currently associated with an OMIM phenotype. Haploinsufficiency of RPS17 due to sequence variants and whole/partial gene deletions are associated with Diamond-Blackfan anemia-4 (DBA4; OMIM 612527), an autosomal dominant disorder mainly characterized by normochromic macrocytic anemia, reticulocytopenia, and nearly absent erythroid progenitors in the bone marrow. Affected individuals show growth retardation, and approximately 30 to 50% have craniofacial, upper limb, heart, and urinary system congenital malformations. However, some patients with DBA4 do not have any clinical manifestations, and symptoms can vary among affected members of the same family. Additionally, larger deletions of the 15q25.2q25.3 recurrent region (LCR A-D) have been reported in individuals with variable phenotypes, including developmental delay, intellectual disability, behavioral abnormalities, psychomotor and language delay, and/or multiple other congenital anomalies (Burgess 2014, Doelken 2013, Palumbo 2012, Wat 2010). While distal 15q25.2q25.3 deletions (LCR C-D) have been proposed as a susceptibility locus for neurodevelopmental and neuropsychiatric disorders, proximal 15q25.2 deletions are typically associated with a more severe phenotype, including mild to moderate intellectual disability, short stature, craniofacial abnormalities, congenital diaphragmatic hernia, cryptorchidism in males, and/or features resembling Diamond-Blackfan anemia. The minimal region of overlap proposed by Burgess et al. and Palumbo et al. (Burgess 2014, Palumbo 2012) for the core features of proximal 15q25.2 deletions partially overlaps the current interval and includes RPS17. References: Burgess et al., Am J Med Genet A. 2014 Jan;164A(1):77-86. PMID: 24352913. Doelken et al., Am J Med Genet A. 2013 Jan;161A(1):218-24. PMID: 23239641. Palumbo et al., Am J Med Genet A. 2012 Dec;158A(12):3182-9. PMID: 23166063. Wat et al., J Med Genet. 2010 Nov;47(11):777-81. PMID: 20921022. |