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| Mendeliome v2.14 | HDAC2 | Lucy Spencer Classified gene: HDAC2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v2.14 | HDAC2 | Lucy Spencer Gene: hdac2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v2.13 | HDAC2 |
Lucy Spencer gene: HDAC2 was added gene: HDAC2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: HDAC2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: HDAC2 were set to 30806031; 27620904; 38753158 Phenotypes for gene: HDAC2 were set to Neurodevelopmental disorder (MONDO:0700092), HDAC2-related Review for gene: HDAC2 was set to GREEN Added comment: PMID: 27620904 In a large syndromic ID cohort one de novo missense in HDAC2 was identified Gly28Asp (filtered out in gnomad). This individual is also present in DECIPHER where the phenotype listed are: hypotonia, autistic behaviour, delayed speech and language development, developmental regression, hyperactivity, intellectual disability, motor stereotypy, and symptomatic seizures. PMID: 30806031 Met31Ile identified as de novo in an individual with a phenotype resembling Cornelia de Lange syndrome - severe developmental delay, limb abnormalities, congenital heart defect, cryptorchidism and hypoplastic genitalia, growth retardation, and characteristic craniofacial features. The variant is absent from gnomad. This individual also had a 5.6Mb copy number gain at 15q11.2q13.1 which is associated with a developmental disorder. PMID: 38753158 An individual clinically diagnosed with Rubenstein Tabi syndrome who had negative genetic testing for known RSTS genes. Phenotype included ID, growth and motor delay, dysmorphisms (synophrys, prominent columella, short philtrum, high nasal root, abnormal ears with prominent antihelix), broad halluces, speech delay, feeding problems and recurrent infections, vertebral anomalies, hypoplasia of corpus callosum, hypermetropia and early puberty. Identified a de novo frameshift p.(K444Lfs*61) in HDAC2 which is an elongation variant. This variant is absent from gnomad but other elongation variants are present with 4-13 hets. The variant was predicted to disrupt the NLS and studies in transfected cells showed protein mislocalisation. HDAC2 protein abundance was also reduced in patient cells, and patient cells showed similar differentially expressed genes to RSTS patients. The two missense are near each other and are present at or near annotated binding sites in DECIPHER, both very well conserved residues and one of the paper described this region as needed for the catalytic activity of the deacetylase. Borderline amber/green due to lack of functional evidence for the missense variants and the presence of other elongation variants in gnomad (however it is unclear if they also affect the NLS). Sources: Literature |
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