ClinVar Miner

Submissions for variant NM_000046.5(ARSB):c.113_121del (p.Gly38_Gly40del) (rs550086186)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America 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 VI 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)
Invitae RCV000586192 SCV001047151 benign not provided 2019-02-15 criteria provided, single submitter clinical testing
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000586192 SCV000800854 uncertain significance not provided 2017-04-12 no assertion criteria provided clinical testing

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