Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Broad Center for Mendelian Genomics, |
RCV000984509 | SCV001132565 | likely pathogenic | Infantile-onset ascending hereditary spastic paralysis | 2018-11-15 | criteria provided, single submitter | research | The homozygous p.Leu352SerfsTer11 variant in ALS2 was identified by our study in one individual with Infantile-Onset Spastic Paraplegia. This variant was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at position 352 and leads to a premature termination codon 11 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the ALS2 gene is an established disease mechanism in autosomal recessive Infantile-Onset Spastic Paraplegia, and this is a loss of function variant. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic. |
Medical Molecular Genetics Department, |
RCV000984509 | SCV002538662 | pathogenic | Infantile-onset ascending hereditary spastic paralysis | criteria provided, single submitter | clinical testing | Homozygous |