ClinGen Dosage Sensitivity Curation Page


Curation Status: Complete

Gene Information

Location Information

Evidence for Loss Phenotypes

Evidence for loss of function phenotype
PubMed ID Description
30269351 Mulhern et al. describe 24 cases with variants of the NBEA gene . Variants include 8 nonsense, 5 frameshift, 4 missense, 5 intragenic deletions , 1 splice site and 1 multigene. Al variants were absent from gnomad and 12,325 controls. Twenty three of the 24 cases had parental follow-up and were de novo. Twenty of 24 of the variants are predicted to result in Loss of function. All patients had neurodevelopmental disease that included developmental delay and or intellectual disability. Half the patients had autism or autistic features and about half the patients had epilepsy. Drosophila and mouse models demonstrate abnormal synaptic growth and impaired physical and social behavior (PMID 26100104, 23153818).
12746398 This paper describes a de novo translocation t(5;13)(q12.1;q13.2) disrupting NBEA in a male with isolated autism. The breakpoint on 13q falls within the second intron of the NBEA gene. No alternative transcripts lacking the first two exons were identified. The authors predicted that the translocation leads to a lack of NBEA expression

Evidence for Triplosenstive Phenotype

NOTE:The loss of function score should be used to evaluate deletions, and the triplosensitivity score should be used to evaluated duplications. CNVs encompassing more than one gene must be evaluated in their totality (e.g. overall size, gain vs. loss, presence of other genes, etc). The rating of a single gene within the CNV should not necessarily be the only criteria by which one defines a clinical interpretation. Individual interpretations must take into account the phenotype described for the patient as well as issues of penetrance and expressivity of the disorder. ACMG has published guidelines for the characterization of postnatal CNVs, and these recommendations should be utilized (Genet Med (2011)13: 680-685). Exceptions to these interpretive correlations will occur, and clinical judgment should always be exercised.