Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Broad Center for Mendelian Genomics, |
RCV003226145 | SCV003922347 | likely pathogenic | Neuronopathy, distal hereditary motor, type 7A | 2023-05-02 | criteria provided, single submitter | curation | The heterozygous c.742-2A>G variant in SLC5A7 was identified by our study in one individual with muscle weakness and easy fatigability. Trio exome analysis showed this variant to be de novo. The c.742-2A>G variant in SLC5A7 has not been previously reported in individuals with distal hereditary motor neuronopathy type VIIa. This variant is absent in population databases. This variant is located in the 3’ splice region. Computational tools do suggest an impact to splicing. However, this information is not predictive enough to determine pathogenicity. Heterozygous loss of function of the SLC5A7 gene is strongly associated to distal hereditary motor neuronopathy type VIIa. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic for autosomal dominant distal hereditary motor neuronopathy type VIIa. ACMG/AMP Criteria applied: PVS1_Strong, PS2_Supporting, PM2_Supporting (Richards 2015). |