Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000370628 | SCV000344411 | likely benign | not specified | 2016-08-30 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000399404 | SCV000372943 | uncertain significance | Niemann-Pick disease, type A | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory 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, this variant 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, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
Labcorp Genetics |
RCV001084821 | SCV000755904 | likely benign | Niemann-Pick disease, type B; Niemann-Pick disease, type A | 2024-01-26 | criteria provided, single submitter | clinical testing | |
Mayo Clinic Laboratories, |
RCV000675398 | SCV000801071 | uncertain significance | not provided | 2023-05-23 | criteria provided, single submitter | clinical testing | BS1 |
Broad Center for Mendelian Genomics, |
RCV001249036 | SCV001422971 | uncertain significance | Sphingomyelin/cholesterol lipidosis | 2020-01-22 | criteria provided, single submitter | curation | The p.Gly530Ala variant in SMPD1 (also known as p.Gly528Ala due to a difference in cDNA numbering) has not been previously reported in individuals with Niemann-Pick disease but has been identified in 0.477% (119/24970) of African chromosomes, 0.023% (8/35428) of African chromosomes, and 0.003% (1/30616) of South Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs35122256). This variant has also been reported in ClinVar (VariationID: 289948) as likely benign by Invitae and EGL Genetic Diagnostics and as a VUS by Illumina Clinical Services Laboratory and Mayo Clinic Genetic Testing Laboratories. The Gly at position 530 is not highly conserved in mammals and evolutionary distant species, and 1 mammal (Prairie Vole) carries an Ala, raising the supporting that this change at this position may be tolerated. Additional computational prediction tools suggest that the variant is less likely to impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, while the clinical significance of the p.Gly530Ala variant is uncertain, these data suggest that it is more likely to be benign. ACMG/AMP Criteria applied: BS1 (Richards 2015). |
Natera, |
RCV000399404 | SCV002092285 | likely benign | Niemann-Pick disease, type A | 2017-11-16 | no assertion criteria provided | clinical testing | |
Prevention |
RCV003930180 | SCV004738326 | likely benign | SMPD1-related disorder | 2021-04-01 | no assertion criteria provided | clinical testing | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). |