Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Diagnostic Laboratory, |
RCV001260833 | SCV001437929 | uncertain significance | Intellectual disability | 2020-09-10 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV001265842 | SCV001444014 | likely pathogenic | Inborn genetic diseases | 2020-07-14 | criteria provided, single submitter | clinical testing | The alteration results in a premature stop codon: The c.6661_6664delTTAG (p.L2221Sfs*10) alteration, located in coding exon 8 of the ZNF292 gene, results from a deletion of 4 nucleotides from positions 6661 to 6664, causing a translational frameshift with a predicted alternate stop codon after 10 amino acids. Frameshifts are typically deleterious in nature; however, this frameshift occurs at the 3' terminus of ZNF292, is not expected to trigger nonsense-mediated mRNA decay, and a truncated mutant protein could still be expressed (Maquat, 2004). This alteration impacts the last 503 amino acids of the protein. Although the exact functional impact of these altered amino acids is unknown at this time, it is predicted that this alteration would remove a significant portion of the protein. The alteration is not observed in population databases: Based on data from the Genome Aggregation Database (gnomAD), the ZNF292 c.6661_6664delTTAG alteration was not observed, with coverage at this position. The alteration has been observed in affected individuals: This alteration was reported as a de novo occurrence in a two-year old female with developmental delay, autism spectrum disorder, speech delay, hypotonia, epilepsy, and ataxia. In a second individual, this variant was reportedly maternally inherited; the mother was reported to have mild intellectual disability (ID) while the index case was a nine-year old boy with ID, epilepsy, partial agenesis of the corpus callosum, nystagmus/strabisumus, and dysmorphic features. Other family members with intellectual disabilities were negative for this alteration (Mirzaa, 2020). Based on the available evidence, this alteration is classified as likely pathogenic. |
| University of Washington Center for Mendelian Genomics, |
RCV001261763 | SCV001439079 | uncertain significance | Neurodevelopmental disorder | no assertion criteria provided | research |