Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV004460083 | SCV004957376 | likely pathogenic | Inborn genetic diseases | 2024-02-01 | criteria provided, single submitter | clinical testing | The c.1823dupA (p.N608Kfs*23) alteration, located in exon 17 (coding exon 17) of the SPAST gene, consists of a duplication of A at position 1823, causing a translational frameshift with a predicted alternate stop codon after 23 amino acids. This alteration occurs at the 3' terminus of the SPAST gene, is not expected to trigger nonsense-mediated mRNA decay and results in the elongation of the protein by 13 amino acids. This frameshift impacts the last 9 amino acids (1.5%) of the native protein. Frameshifts are typically deleterious in nature and the impacted region is critical for protein function (Ambry internal data). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). Based on the available evidence, this alteration is classified as likely pathogenic. |