Submissions for variant NM_002076.4(GNS):c.198G>A (p.Pro66=)

gnomAD frequency: 0.70681  dbSNP: rs1147096

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000079972	SCV000111863	benign	not specified	2014-06-03	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000079972	SCV000308697	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000616982	SCV000380845	benign	Mucopolysaccharidosis, MPS-III-D	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 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589399	SCV000697909	benign	not provided	2016-12-04	criteria provided, single submitter	clinical testing	Variant summary: The c.198G>A (p.Pro66=) in GNS gene is a synonymous change that involves a non-conserved nucleotide. 5/5 programs in Alamut predict that this variant does not affect normal splicing, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in the control population dataset of ExAC at a frequency of 0.0655 (75159/114750 chrs tested), indicating that it is an ancestral allele. The observed frequency exceeds the maximum expected allele frequency for a pathogenic GNS variant of 0.0011 suggesting that it is a benign polymorphism. The variant of interest has been reported as Benign by a reputable database/clinical laboratory. Taking together, based on the prevalence in general population the variant was classified as Benign.
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000616982	SCV000744952	benign	Mucopolysaccharidosis, MPS-III-D	2015-09-21	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000616982	SCV001724468	benign	Mucopolysaccharidosis, MPS-III-D	2024-02-01	criteria provided, single submitter	clinical testing
Pars Genome Lab	RCV000616982	SCV001750040	benign	Mucopolysaccharidosis, MPS-III-D	2021-07-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000589399	SCV001861970	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000616982	SCV001933878	benign	Mucopolysaccharidosis, MPS-III-D	2021-08-10	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000589399	SCV005229037	benign	not provided		criteria provided, single submitter	not provided
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000616982	SCV000733185	benign	Mucopolysaccharidosis, MPS-III-D		no assertion criteria provided	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000589399	SCV000801374	benign	not provided	2015-10-20	no assertion criteria provided	clinical testing
Natera, Inc.	RCV001274497	SCV001458726	benign	Sanfilippo syndrome	2020-09-16	no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000079972	SCV001925864	benign	not specified		no assertion criteria provided	clinical testing