Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV001009230 | SCV001169050 | pathogenic | not provided | 2019-01-22 | criteria provided, single submitter | clinical testing | The c.1939delG variant causes a frameshift starting with codon Alanine 647, changes this amino acid to a Histidine residue, and creates a premature Stop codon at position 5 of the new reading frame, denoted p.Ala647HisfsX5. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.1939delG variant is not observed in large population cohorts (Lek et al., 2016). Although the c.1939delG has not been reported previously to our knowledge, other loss-of-function variants in the SPG7 gene have been reported in the Human Gene Mutation Database in association with SPG7-related disorders (Stenson et al., 2014). |
| Labcorp Genetics |
RCV001860602 | SCV002239054 | pathogenic | Hereditary spastic paraplegia 7 | 2021-06-24 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ala647Hisfs*5) in the SPG7 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SPG7 are known to be pathogenic (PMID: 21623769, 22964162). This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SPG7-related conditions. ClinVar contains an entry for this variant (Variation ID: 817991). For these reasons, this variant has been classified as Pathogenic. |
| 3billion | RCV001860602 | SCV002572562 | pathogenic | Hereditary spastic paraplegia 7 | 2022-09-01 | criteria provided, single submitter | clinical testing | The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: <0.001%). This variant on the canonical splice site is predicted to alter splicing, resulting in a loss or disruption of normal protein function. Multiple pathogenic loss-of-function variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic without evidence for the classification (ClinVar ID: VCV000817991). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. |