Submissions for variant NM_000543.5(SMPD1):c.107_112del (p.Val36_Leu37del)

dbSNP: rs775860642

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000398424	SCV000372920	uncertain significance	Sphingomyelin/cholesterol lipidosis	2016-06-14	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000954959	SCV001101627	benign	Niemann-Pick disease, type B; Niemann-Pick disease, type A	2025-01-21	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000252024	SCV002500210	benign	not specified	2022-03-08	criteria provided, single submitter	clinical testing	Variant summary: SMPD1 c.107_112delTGCTGG (p.Val36_Leu37del) results in an in-frame deletion that is predicted to remove two amino acids from the encoded protein. The variant allele was found at a frequency of 0.0026 in 232506 control chromosomes, predominantly at a frequency of 0.0038 within the South Asian subpopulation in the gnomAD database, including 1 homozygotes. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 1.7 fold of the estimated maximal expected allele frequency for a pathogenic variant in SMPD1 causing Niemann-Pick Disease phenotype (0.0022), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Two classified as benign/likely benign while one classified as VUS. Based on the evidence outlined above, the variant was classified as benign.
CeGaT Center for Human Genetics Tuebingen	RCV001729484	SCV004135837	likely benign	not provided	2024-07-01	criteria provided, single submitter	clinical testing	SMPD1: PM4, BS2
PreventionGenetics, part of Exact Sciences	RCV003891855	SCV000305086	likely benign	SMPD1-related disorder	2021-03-15	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).
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001729484	SCV001978708	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001729484	SCV001980388	likely benign	not provided		no assertion criteria provided	clinical testing
Natera, Inc.	RCV001828137	SCV002091658	likely benign	Niemann-Pick disease, type A	2017-08-10	no assertion criteria provided	clinical testing