Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
New York Genome Center | RCV003448639 | SCV004176213 | uncertain significance | Neurodevelopmental disorder with language delay and behavioral abnormalities, with or without seizures | 2023-08-18 | criteria provided, single submitter | clinical testing | The de novo c.1136G>A p.(Arg379His) variant identified in the AGO1 gene has not previously been reported in the literature or public variant repositories (ClinVar and LOVD) and is absent from population databases (gnomAD v2.1.1 and v3.1.2, TOPMed Freeze 8), suggesting it is not a common benign variant in the populations represented in those databases. The c.1136G>A variant in AGO1 is located in exon 9 (just 4 nucleotides away from exon/intron boundary) of this 19-exon gene and predicted to replace an evolutionarily conserved arginine amino acid with histidine at position 379 in the linker 2 (L2) domain of the encoded protein. In silico predictions are inconclusive of the variant's damaging effect [REVEL = 0.342, SpliceAI score = 0.00]; however, there are no functional studies to support or refute these predictions. Based on available evidence this de novo c.1136G>A, p. (Arg379His) variant identified in AGO1 is classified as a Variant of Uncertain Significance. |