Submissions for variant NM_000528.4(MAN2B1):c.1010G>A (p.Arg337Gln)

gnomAD frequency: 0.34583  dbSNP: rs1133330

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000079070	SCV000110939	benign	not specified	2015-04-24	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000079070	SCV000304694	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000298455	SCV000410801	benign	Deficiency of alpha-mannosidase	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.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000079070	SCV000539581	benign	not specified	2016-03-28	criteria provided, single submitter	clinical testing	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency, ClinVar assertions are B/LB
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000079070	SCV000919597	benign	not specified	2017-11-07	criteria provided, single submitter	clinical testing	Variant summary: The MAN2B1 c.1010G>A (p.Arg337Gln) variant involves the alteration of a non-conserved nucleotide. 4/4 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 85845/277142 control chromosomes (30 homozygotes) at a frequency of 0.309751, which is approximately 196 times the estimated maximal expected allele frequency of a pathogenic MAN2B1 variant (0.0015811), suggesting this variant is likely a benign polymorphism. This variant has been reported in affected individuals co-occuring with pathogenic mutations and is listed as polymorphism by authors (Sbaragli_2005). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. Taken together, this variant is classified as benign.
GeneDx	RCV000675484	SCV000986642	benign	not provided	2018-06-13	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000298455	SCV001717966	benign	Deficiency of alpha-mannosidase	2024-02-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000298455	SCV001738066	benign	Deficiency of alpha-mannosidase	2021-06-10	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000675484	SCV005314694	benign	not provided		criteria provided, single submitter	not provided
Genetic Services Laboratory, University of Chicago	RCV000079070	SCV000151814	likely benign	not specified		no assertion criteria provided	clinical testing	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000298455	SCV000733846	benign	Deficiency of alpha-mannosidase		no assertion criteria provided	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000675484	SCV000801174	benign	not provided	2015-10-23	no assertion criteria provided	clinical testing
Natera, Inc.	RCV000298455	SCV001454357	benign	Deficiency of alpha-mannosidase	2020-09-16	no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000079070	SCV001922299	benign	not specified		no assertion criteria provided	clinical testing