Submissions for variant NM_000046.5(ARSB):c.113_121del (p.Gly38_Gly40del)

dbSNP: rs550086186

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000855567	SCV000694146	benign	not specified	2019-07-18	criteria provided, single submitter	clinical testing	Variant summary: ARSB c.113_121delGCGCCGGGG (p.Gly38_Gly40del) results in an in-frame deletion that is predicted to remove three amino acids from the encoded protein. The variant allele was found at a frequency of 0.0021 in 123320 control chromosomes, predominantly at a frequency of 0.014 within the South Asian subpopulation in the gnomAD database, including 6 homozygotes. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 6 fold of the estimated maximal expected allele frequency for a pathogenic variant in ARSB causing Mucopolysaccharidosis Type VI (Maroteaux-Lamy Syndrome) phenotype (0.0022), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. The variant, c.113_121delGCGCCGGGG has been reported in the literature in a homozygous individual affected with Mucopolysaccharidosis Type VI, with an attenuated disease severity (Mathew_2015). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two other submitters have provided clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (1x benign and 1x uncertain significance). Based on the evidence outlined above, the variant was classified as benign.
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova	RCV000677450	SCV000802953	benign	Mucopolysaccharidosis type 6	2018-01-01	criteria provided, single submitter	curation	In frame deletion in a repetitive region without a known function (BP3); Allele frequency greater than expected for disorder (BS1). Homozygotes reported in ExAC (BS2)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000677450	SCV001047151	benign	Mucopolysaccharidosis type 6	2024-01-26	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000677450	SCV001737265	benign	Mucopolysaccharidosis type 6	2021-05-18	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000677450	SCV002795837	likely benign	Mucopolysaccharidosis type 6	2022-05-17	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000586192	SCV004163003	benign	not provided	2023-03-01	criteria provided, single submitter	clinical testing	ARSB: BS1, BS2
Mayo Clinic Laboratories, Mayo Clinic	RCV000586192	SCV000800854	uncertain significance	not provided	2017-04-12	no assertion criteria provided	clinical testing
Natera, Inc.	RCV000677450	SCV001458082	benign	Mucopolysaccharidosis type 6	2020-05-01	no assertion criteria provided	clinical testing