Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000674668 | SCV000800047 | likely pathogenic | Niemann-Pick disease, type A | 2018-05-18 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
RCV000674668 | SCV000914523 | uncertain significance | Niemann-Pick disease, type A | 2017-07-11 | criteria provided, single submitter | clinical testing | The SMPD1 c.56delA (p.Gln19ArgfsTer58) variant results in a frameshift, and is predicted to result in premature termination of the protein. It was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018) and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score for this variant, it could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene and cDNA change, and amino acid change. No publications were found based on this search. Due to the potential impact of frameshift variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for SMPD1-related disorders. |
| Invitae | RCV003768012 | SCV004588101 | pathogenic | Niemann-Pick disease, type B; Niemann-Pick disease, type A | 2023-01-23 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with SMPD1-related conditions. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 558404). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln19Argfs*58) in the SMPD1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SMPD1 are known to be pathogenic (PMID: 12369017, 15221801). |