Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000780735 | SCV000918247 | pathogenic | not specified | 2017-09-12 | criteria provided, single submitter | clinical testing | Variant summary: The SMPD1 c.564dupC (p.Lys189GlnfsX4) variant results in a premature termination codon, predicted to cause a truncated or absent SMPD1 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as likely pathogenic/pathogenic by our laboratory (e.g. c.573delT (p.Ser192fsX65), c.996delC (p.Phe333fsX52), and c.1785_1786delTT (p.Ala597fsX7))). This variant was found in 214/167462 control chromosomes at a frequency of 0.0012779, which does not exceed the estimated maximal expected allele frequency of a pathogenic SMPD1 variant (0.0022361) and was considered a low quality site (via gnomAD), therefore making this data less reliable. A publication, Ding_2016, reports the variant in a compound heterozygote individual dx with NPDA, while Ranganath_2016 and Pittis_2004 reports the variant in compound heterozygote individuals dx with NPDB. In an in vitro study, enzyme activity in transfected cells was non-detectable, compared to WT (Dardis_2005). In addition, a clinical diagnostic laboratory classified this variant as pathogenic. Taken together, this variant is classified as pathogenic. |
| Labcorp Genetics |
RCV002535682 | SCV003516388 | pathogenic | Niemann-Pick disease, type B; Niemann-Pick disease, type A | 2022-04-11 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 632992). This premature translational stop signal has been observed in individual(s) with SMPD1-related conditions (PMID: 27338287). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change creates a premature translational stop signal (p.Lys189Glnfs*4) 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). |
| Department of Pathology and Laboratory Medicine, |
RCV005359522 | SCV005915097 | likely pathogenic | Acid sphingomyelinase deficiency | 2023-01-26 | criteria provided, single submitter | research |