Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Diagnostics Services |
RCV001799542 | SCV002043741 | uncertain significance | Hereditary spastic paraplegia 48 | 2021-06-16 | criteria provided, single submitter | clinical testing | The c.869G>A variant is not present in publicly available population databases like 1000 Genomes and Exome Variant Server (EVS). The heterozygous state of the variant is present in Exome Aggregation Consortium (ExAC), Genome Aggregation Database (gnomAD) and dbSNP at a very low frequency. The variant is not present in Indian Exome Database and in our in-house exome database. The variant was not earlier reported to ClinVar, Human Genome Mutation Database (HGMD) and/or OMIM databases in any affected individuals. Prediction from different in-silico pathogenicity prediction programs like SIFT, PolyPhen-3, MutationTaster2, CADD, Varsome etc. are contradictory. Due to lack of enough evidence the variant has been classified as uncertain significance. |
| Victorian Clinical Genetics Services, |
RCV001799542 | SCV002767677 | uncertain significance | Hereditary spastic paraplegia 48 | 2020-05-21 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as VUS – 3C. Following criteria are met: 0102 - Loss-of-function is a known mechanism of disease for this gene. (N) 0106 - This gene is known to be associated with autosomal recessive disease. (N) 0200 - Variant is predicted to result in a missense amino acid change from arginine to glutamine. (N) 0251 - Variant is heterozygous. (N) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (2 Het, 0 Hom). (P) 0309 - An alternative amino acid change at the same position has been observed in gnomAD (7 Het, 0 Hom). (N) 0503 - Missense variant consistently predicted to be tolerated or not conserved in mammals with a minor amino acid change. (B) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (N) 0708 – A comparable variant has been previously reported as a VUS (ClinVar) (N) 0807 - Variant has not previously been reported in a clinical context. (N) 0905 - No segregation evidence has been identified for this variant. (N) 1007 - No published functional evidence has been identified for this variant. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign |
| Ambry Genetics | RCV004953068 | SCV005454126 | likely benign | Inborn genetic diseases | 2024-07-05 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |