Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute of Human Genetics, |
RCV002267589 | SCV002549715 | likely pathogenic | Bryant-Li-Bhoj neurodevelopmental syndrome 2 | 2023-01-31 | criteria provided, single submitter | clinical testing | The variant c.68C>G (p.(Thr23Arg)) in exon 2 of the H3-3B-gene is not found in in the gnomAD database. Another nucleotide change resulting in another amino acid change at the same position was described as pathogenic (c.68C>A, p.(Thr23Lys); PMID: 34876591), although functional studies did not reveal a pathogenic influence of the published variant on protein function. The variant affects a highly conserved nucleotide, a highly conserved amino acid, there is a moderate physicochemical difference between Thr and Arg and the variant is located within a protein domain. This variant has a pathogenic computational verdict based on in silico prediction programs. Missense variants in H3-3B are a known mechanism of disease. It was found de novo in our patient. Thus, we consider this H3-3B-variant a likely pathogenic variant. ACMG criteria used for classification: PM2, PM5, PM6, PP2, PP3. |