Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| New York Genome Center | RCV000207520 | SCV001480234 | pathogenic | Syndromic X-linked intellectual disability 34 | 2019-08-28 | criteria provided, single submitter | clinical testing | The de novo c.1394dup (p.Asn466LysfsTer13) variant identified in the NONO gene leads to a frameshift of the protein at amino acid 466/472 (coding exon 11/11). This variant is absent from gnomAD and ExAC, suggesting it is not a common benign variant in the populations represented in these databases. It is reported in ClinVar as Pathogenic (VarID:222082) based on literature evidence. The c.1394dup (p.Asn466LysfsTer13) variant has been reported in two affected individuals in the literature [PMID: 27550220; PMID: 26571461] including a 5y male with hypotonia, global developmental delay, dysmorphic features and left ventricular non-compaction [PMID: 27550220]. Immunoblot and immunocytochemistry studies using skin fibroblasts from an affected male demonstrated that the p.Asn466LysfsTer13 variant results in nearly undetectable levels of NONO [PMID: 26571461]. Given the presence of this variant in 2 affected individuals in the literature, its absence in population databases, its presence de novo in this individual, and near absence of NONO protein in fibroblasts of a patient reported in the literature, the c.1394dup (p.Asn466LysfsTer13) variant identified in this individual is reported here as Pathogenic. |
| OMIM | RCV000207520 | SCV000263073 | pathogenic | Syndromic X-linked intellectual disability 34 | 2021-08-20 | no assertion criteria provided | literature only |