Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute of Medical Genetics and Applied Genomics, |
RCV001268116 | SCV001446773 | likely pathogenic | not provided | 2020-10-23 | criteria provided, single submitter | clinical testing | |
Broad Institute Rare Disease Group, |
RCV002537706 | SCV003761136 | uncertain significance | Leukoencephalopathy-ataxia-hypodontia-hypomyelination syndrome | 2023-01-24 | criteria provided, single submitter | curation | The c.1572+1G>T variant in POLR3A has not been previously reported in the literature in individuals with POLR3A-related disorders, but has been identified in 0.003% (1/34590) of Latino/Admixed American chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs141484643). Although this variant has been seen in the general population in a heterozygous state, its frequency is low enough to be consistent with a recessive carrier frequency. This variant has also been reported in ClinVar (Variation ID#: 986937) and has been interpreted as likely pathogenic by CeGaT Center for Human Genetics Tübingen. This variant is located in the 3' splice region. Computational predict a splicing impact, though this information is not predictive enough to determine pathogenicity. This variant is adjacent to an in-frame exon and is more likely to escape nonsense mediated decay (NMD) and result in a truncated protein. In summary, the clinical significance of the c.1572+1G>T variant is uncertain. ACMG/AMP Criteria applied: PVS1_moderate, PM2_supporting (Richards 2015). |