Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002570572 | SCV003509210 | pathogenic | Sphingolipid activator protein 1 deficiency | 2023-12-09 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Asp272Glufs*29) in the PSAP gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PSAP are known to be pathogenic (PMID: 8554069, 11309366, 17616409, 19267410, 30632081). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PSAP-related conditions. ClinVar contains an entry for this variant (Variation ID: 977281). For these reasons, this variant has been classified as Pathogenic. |
| Clinical Genomics Laboratory, |
RCV001254872 | SCV001427071 | likely pathogenic | not provided | 2019-08-08 | no assertion criteria provided | clinical testing | The p.Asp272Glufs*29 variant in the PSAP gene has not been previously reported in association with disease. This variant has been identified in 1/16,256 African chromosomes by the Genome Aggregation Database (http://gnomad.broadinstitute.org/).The p.Asp272Glufs*29 variant results in a 8bp deletion, which causes a shift in the protein reading frame, leading to a premature termination codon 29 amino acids downstream. Loss of function is an established mechanism of disease for the PSAP gene. These data were assessed using the ACMG/AMP variant interpretation guidelines. In summary, there is sufficient evidence to classify the p.Asp272Glufs*29 variant as likely pathogenic for saposin deficiencies in an autosomal recessive manner based on the information above. [ACMG evidence codes used: PVS1; PM2] |