Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Neuberg Centre For Genomic Medicine, |
RCV003389370 | SCV004101475 | uncertain significance | Hereditary spastic paraplegia 11 | criteria provided, single submitter | clinical testing | The missense variant p.P2345S in SPG11 (NM_025137.4) has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.P2345S variant is observed in 3/30,614 (0.0098%) alleles from individuals of South Asian background in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. There is a moderate physicochemical difference between proline and serine. The p.P2345S missense variant is predicted to be damaging by both SIFT and PolyPhen2. The proline residue at codon 2345 of SPG11 is conserved in all mammalian species. The nucleotide c.7033 in SPG11 is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance. |