Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Breda Genetics srl | RCV001352898 | SCV001547508 | likely pathogenic | Hereditary spastic paraplegia 45 | 2019-03-05 | criteria provided, single submitter | clinical testing | The variant c.1449+2T>C in the NT5C2 gene affects the donor splice site of intron 18 and is therefore highly likely to impact the splicing process by causing the retention of the following intron and the formation of an aberrant mRNA, which is unlikely to be exported and translated into protein. The variant is reported with an estimated allele frequency of 0.000004 in gnomAD exomes (1/249214 alleles) with no homozygous individuals reported. The mutational spectrum of spinocerebellar ataxia 45 includes both protein-disrupting and missense variants. |
Laboratory of Molecular Genetics |
RCV002276708 | SCV002564494 | pathogenic | Neurodevelopmental disorder | 2023-01-17 | criteria provided, single submitter | clinical testing | |
3billion, |
RCV001352898 | SCV003841869 | likely pathogenic | Hereditary spastic paraplegia 45 | 2023-02-23 | 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 was predicted to alter splicing and result in a loss or disruption of normal protein function. The predicted truncated protein may be shortened by more than 10%. The variant has been reported at least twice as pathogenic without evidence for the classification (ClinVar ID: VCV001048080). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline. |