Submissions for variant NM_000487.6(ARSA):c.1055A>G (p.Asn352Ser)

gnomAD frequency: 0.19530  dbSNP: rs2071421

Total submissions: 19

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000078931	SCV000110791	other	not provided	2018-07-24	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000249834	SCV000304453	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000020310	SCV000439433	benign	Metachromatic leukodystrophy	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.
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000078931	SCV000511542	benign	not provided	2016-10-11	criteria provided, single submitter	clinical testing
SIB Swiss Institute of Bioinformatics	RCV000020310	SCV000883252	benign	Metachromatic leukodystrophy	2018-10-15	criteria provided, single submitter	curation	This variant is interpreted as Benign - Stand Alone, for Metachromatic leukodystrophy, autosomal recessive. The following ACMG Tag(s) were applied: BA1 => Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. BP4 => Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.). BS3 => Well-established in vitro or in vivo functional studies show no damaging effect on protein function or splicing (https://www.ncbi.nlm.nih.gov/pubmed/11941485) (https://www.ncbi.nlm.nih.gov/pubmed/2574462).
Mendelics	RCV000020310	SCV001141462	likely benign	Metachromatic leukodystrophy	2019-05-28	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000020310	SCV001733012	benign	Metachromatic leukodystrophy	2025-02-04	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000020310	SCV001737289	benign	Metachromatic leukodystrophy	2021-06-10	criteria provided, single submitter	clinical testing
GeneDx	RCV000078931	SCV001871299	benign	not provided	2021-11-11	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 2574462, 21648305, 8897113, 30026549, 32437521, 26577183, 31670782, 32470555, 31312839, 31694723, 23581857)
Breakthrough Genomics, Breakthrough Genomics	RCV000078931	SCV005207843	likely benign	not provided		criteria provided, single submitter	not provided
OMIM	RCV000020310	SCV000023349	benign	Metachromatic leukodystrophy	1997-12-01	no assertion criteria provided	literature only
GeneReviews	RCV000020310	SCV000040685	not provided	Metachromatic leukodystrophy		no assertion provided	literature only
Natera, Inc.	RCV000020310	SCV001456232	benign	Metachromatic leukodystrophy	2019-12-10	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001357207	SCV001552597	uncertain significance	Metachromatic leukodystrophy, juvenile type		no assertion criteria provided	clinical testing	ClinVar reports this variant as a Pseudodeficiency allele from ClinVar. Homozygosity for the p.Asn350Ser variant alone results in 50% or more of the mean control ARSA enzyme activity in leukocytes. Allele frequency is common in at least one population database (frequency: 39.478% in ExAC) based on the frequency threshold of 1.151% for this gene.Variant was observed in a homozygous state in population databases more than expected for disease.This variant is interpreted as Benign - Stand Alone, for Metachromatic leukodystrophy, autosomal recessive. The following ACMG Tag(s) were applied: BA1 => Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. BP4 => Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.). BS3 => Well-established in vitro or in vivo functional studies show no damaging effect on protein function or splicing (https://www.ncbi.nlm.nih.gov/pubmed/11941485) (https://www.ncbi.nlm.nih.gov/pubmed/2574462). (ClinVar: SIB Swiss Institute of Bioinformatics)
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000249834	SCV001740695	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000249834	SCV001925236	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000249834	SCV001931644	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000249834	SCV001954847	benign	not specified		no assertion criteria provided	clinical testing
Gelb Laboratory, University of Washington	RCV000020310	SCV005046796	not provided	Metachromatic leukodystrophy		no assertion provided	in vitro