Submissions for variant NM_000543.5(SMPD1):c.1522G>A (p.Gly508Arg)

gnomAD frequency: 0.19762  dbSNP: rs1050239

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000079195	SCV000111064	benign	not specified	2015-04-27	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000079195	SCV000305092	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000336908	SCV000372942	benign	Niemann-Pick disease, type A	2018-03-06	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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000079195	SCV000540393	benign	not specified	2016-03-28	criteria provided, single submitter	clinical testing	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000588146	SCV000697413	benign	not provided	2016-09-05	criteria provided, single submitter	clinical testing	Variant Summary: The c.1522G>A in SMPD1 gene is a missense change that involves the alteration of a mildly conserved nucleotide and 3/5 in silico tools predict benign outcome. The variant was observed in the large and broad cohorts of the ExAC project at an allele frequency of 0.19 (23261/121314 chrs tested). This frequency exceeds the maximal expected allele frequency for a pathogenic variant in this gene (0.002). A reputable database/diagnostic center has classified the variant of interest as Benign. Taking together, based on the prevalence in general population, the variant was classified as Benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001511035	SCV001718210	benign	Niemann-Pick disease, type B; Niemann-Pick disease, type A	2024-02-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000336908	SCV001749175	benign	Niemann-Pick disease, type A	2021-07-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001533322	SCV001749176	benign	Niemann-Pick disease, type B	2021-07-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000588146	SCV001859514	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 24977483)
Breakthrough Genomics, Breakthrough Genomics	RCV000588146	SCV005323430	benign	not provided		criteria provided, single submitter	not provided
Mayo Clinic Laboratories, Mayo Clinic	RCV000588146	SCV000801069	benign	not provided	2015-12-15	no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000079195	SCV001743261	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000079195	SCV001953051	benign	not specified		no assertion criteria provided	clinical testing
Natera, Inc.	RCV000336908	SCV002092282	benign	Niemann-Pick disease, type A	2017-05-06	no assertion criteria provided	clinical testing