Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Breda Genetics srl | RCV001267826 | SCV001445999 | uncertain significance | Neurodevelopmental disorder with or without anomalies of the brain, eye, or heart | 2020-09-15 | criteria provided, single submitter | clinical testing | The variant c.3466G>T (p.Gly1156Trp) in the RERE gene has not been reported in dbSNP, gnomAD, 1000 Genomes, NHLI Exome Sequencing Project (ESP) or ClinVar. The nucleotide position is highly conserved across 35 mammalian species (GERP RS: 5.56). In silico analysis indicates that the variant might be damaging. Another de novo pathogenic missense variant, affecting the same nucleotide position, c.3466G>A (p.Gly1156Arg), has been reported by Fregeau et al. (2016) in a child with intrauterine growth retardation, global developmental delay, mild spastic quadriparesis, dysarthric speech, swallowing difficulties, bilateral optic colobomas and other eye abnormalities, mild sensorineural hearing loss, and brain MRI abnormalities (PMID: 27087320). Based on ACMG variant interpretation guidelines, we classify this variant as uncertain. However, based on the aforementioned evidence, there is a given likelihood that the variant may actually be pathogenic, even if we cannot exclude that it is a rare benign variant. |