Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001267042 | SCV001445223 | likely pathogenic | Inborn genetic diseases | 2020-05-07 | criteria provided, single submitter | clinical testing | The alteration results in an amino acid change: The c.3368G>A (p.R1123Q) alteration is located in coding exon 20 of the POLR2A gene. This alteration results from a G to A substitution at nucleotide position 3368, causing the arginine (R) at amino acid position 1123 to be replaced by a glutamine (Q). The alteration is not observed in population databases: Based on data from the Genome Aggregation Database (gnomAD), the POLR2A c.3368G>A alteration was not observed, with coverage at this position. The alteration has been observed in affected individuals: This alteration has been reported as a de novo occurrence in an individual with developmental delay and hypotonia (Firth, 2009). In addition, an alteration at the same codon, c.3367C>G (p.R1123G), was de novo in an individual with developmental delay, epilepsy, agenesis of the corpus callosum, cortical vision impairment, and hearing loss (Ambry internal data). The altered amino acid is conserved throughout evolution: The p.R1123 amino acid is conserved in available vertebrate species. The alteration is predicted deleterious by in silico modeling: The p.R1123Q alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as likely pathogenic. |