Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Victorian Clinical Genetics Services, |
RCV004789961 | SCV005398483 | uncertain significance | Autosomal recessive complex spastic paraplegia type 9B | 2020-06-11 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.2, this variant is classified as 3B-VUS. Following criteria are met: 0103 - Dominant negative and loss of function are known mechanisms of disease in this gene and are associated with spastic paraplegia. Dominant negative variants are observed in dominant inheritance, whereas loss of function variants result the recessive form of disease (OMIM). (I) 0108 - This gene is associated with both recessive and dominant disease. Variants in ALDH18A1 have been shown to cause both dominant and recessive cutis laxa and spastic paraplegia, although no clear genotype-phenotype correlations have been observed (OMIM). (I) 0200 - Variant is predicted to result in a missense amino acid change from valine to alanine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0309 - An alternative amino acid change at the same position has been observed in gnomAD (v2) (1 heterozygote, 0 homozygotes). (I) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1205 - This variant has been shown to be maternally inherited (by trio analysis). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |