Activity
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15 actions
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| Intellectual disability v2.787 | NBEA | Ivone Leong Classified gene: NBEA as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.787 | NBEA | Ivone Leong Added comment: Comment on list classification: New gene added by external expert and reviewed by curation team: After discussion with the Genomics England Clinical team, there is sufficient evidence has been provided by the external expert review for this gene to be rated green. NBEA is not associated with any phenotypes on OMIM and Gene2Phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.787 | NBEA | Ivone Leong Gene: nbea has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.778 | NBEA | Ivone Leong Classified gene: NBEA as No list | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.778 | NBEA | Ivone Leong Gene: nbea has been removed from the panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.777 | NBEA | Ivone Leong Deleted their review | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.777 | NBEA | Ivone Leong Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.755 | NBEA | Ivone Leong Classified gene: NBEA as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.755 | NBEA | Ivone Leong Added comment: Comment on list classification: New gene added by external expert and reviewed by curation team: Sufficient evidence has been provided by the external expert review for this gene to be rated green. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.755 | NBEA | Ivone Leong Gene: nbea has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.745 | NBEA | Ivone Leong Phenotypes for gene: NBEA were changed from Global developmental delay; Intellectual disability; Seizures to Global developmental delay; Intellectual disability; Seizures; No OMIM number | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.679 | NBEA | Ivone Leong Publications for gene: NBEA were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.510 | NBEA | Konstantinos Varvagiannis reviewed gene: NBEA: Rating: GREEN; Mode of pathogenicity: None; Publications: 30269351, 28554332, 12746398, 12826745, 11450821, 3377648, 23277425, 22109531, 23153818; Phenotypes: Global developmental delay, Intellectual disability, Seizures; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.510 | NBEA | Konstantinos Varvagiannis Deleted their review | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.510 | NBEA |
Konstantinos Varvagiannis gene: NBEA was added gene: NBEA was added to Intellectual disability. Sources: Literature,Expert Review Mode of inheritance for gene: NBEA was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: NBEA were set to Global developmental delay; Intellectual disability; Seizures Penetrance for gene: NBEA were set to unknown Review for gene: NBEA was set to GREEN gene: NBEA was marked as current diagnostic Added comment: PMID: 30269351 is a collaborative study reporting in 24 individuals with pathogenic de novo variants affecting NBEA. All subjects presented with neurodevelopmental disorder including developmental delay or intellectual disability. Half of the patients (12/24) had autistic features or autism. Epilepsy was a feature in 15/24 (62.5%) of patients with onset before the age of 4 years in the majority (approx. 85%). Of the 15 patients with seizures, 80% presented with generalized seizures of variable type (myoclonic, atonic and/or myoclonic-atonic, absence, tonic, clonic or tonic-clonic), 6.67% with focal seizures only and 13.33% with unclassified seizure type. Other features included developmental microcephaly (or borderilne microcephaly) in 3/24 individuals or developmental regression in 2/24. Among the variants identified: 8/24 were stopgain SNVs 5/24 were frameshift 4/24 were missense SNVs 1/24 was a splice site SNV 5/24 concerned an intragenic NBEA deletion 1/24 concerned a 2.87 Mb deletion spanning NBEA as well as additional genes (none of latter associated with disease in OMIM). Two of these individuals were reported in a previously published study of children with DD/ID (PMID: 28554332). Individuals with developmental disorders and de novo coding mutations in NBEA have been reported in further publications including the DDD study (PMID: 28135719 - subject DDD4K.01714), most summarized in the denovo-db (http://denovo-db.gs.washington.edu/denovo-db/QueryVariantServlet?searchBy=Gene&target=NBEA). As also commented in the article, a patient with autism and a de novo balanced translocation disrupting NBEA has been reported (PMID: 12746398) as has also been the case with other deletions spanning NBEA (PMIDs: 12826745, 11450821, 3377648). Previous studies have suggested a role for NBEA in regulation of synaptic structure and function (PMID: 23277425,22109531) as well as a role of neurobeachin in autism-like behaviors in mice (PMID: 23153818). NBEA is intolerant to loss-of-function mutations (pLI=1 in ExAC). Most variants in the study predict loss-of-function. As a result happloinsufficiency seems to be the underlying mechanism. As the authors propose, loss-of-function variants might be associated with more specific (eg. microcephaly or myoclonic-atonic seizures) or severe phenotypic presentations, although the size of the cohort did not not allow safe conclusions. // NBEA is included in DD/ID (but not epilepsy) gene panels offered by different diagnostic labs. // As a result this gene can be considered for inclusion as green in the intellectual disability and epilepsy panels. Sources: Literature, Expert Review |
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