Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
3billion | RCV001807941 | SCV002058244 | pathogenic | Succinate-semialdehyde dehydrogenase deficiency | 2022-01-03 | criteria provided, single submitter | clinical testing | Canonical splice site: predicted to alter splicing and result in a loss or disruption of normal protein function through protein truncation. Multiple pathogenic variants are reported in the predicted truncated region (PVS1_VS). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000004, PM2_M).Each parent is heterozygous for the variant (PM3_P, 3billion dataset). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. |
Neuberg Centre For Genomic Medicine, |
RCV001807941 | SCV004048386 | uncertain significance | Succinate-semialdehyde dehydrogenase deficiency | criteria provided, single submitter | clinical testing | The splice donor variant c.1343+1delG in ALDH5A1 (NM_001080.3) variant has been submitted to ClinVar as Pathogenic but no details available for independent assessment. The variant has not been reported in affected indviduals. The c.1343+1delG variant is observed in 1/30,616 (0.0033%) alleles from individuals of South Asian background in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. The c.1343+1delG variant is a loss of function variant in the gene ALDH5A1, which is intolerant of Loss of Function variants. Since this variant is present in the penultimate exon it is classified as Variant of Uncertain Significance (VUS). Functional studies will be required to prove protein truncation and loss of function. |