Submissions for variant NM_002294.3(LAMP2):c.-4G>C

dbSNP: rs200297370

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000037404	SCV000061061	uncertain significance	not specified	2012-10-16	criteria provided, single submitter	clinical testing	The -4G>C variant in LAMP2 has not been reported in the literature nor previousl y identified by our laboratory. This variant has been identified in 1/6723 Europ ean American chromosomes from a broad population by the NHLBI Exome Sequencing P roject (http://evs.gs.washington.edu/EVS/; dbSNP rs200297370). This variant is l ocated in the 5' UTR of the LAMP2 gene. Although this region can contain regulat ory elements, there is no obvious predicted effect of this variant and there are no other pathogenic variants that have been reported in the 5'UTR region of the LAMP2 gene. In summary, additional information is needed to fully assess the cl inical significance of the -4G>C variant.
GeneDx	RCV000037404	SCV000170077	benign	not specified	2013-07-30	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.
Illumina Laboratory Services, Illumina	RCV000307020	SCV000481615	uncertain significance	Hypertrophic cardiomyopathy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000341633	SCV000481616	benign	Danon disease	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.
Ambry Genetics	RCV000618305	SCV000740144	benign	Cardiovascular phenotype	2017-04-13	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
CeGaT Center for Human Genetics Tuebingen	RCV001725947	SCV002546192	likely benign	not provided	2022-04-01	criteria provided, single submitter	clinical testing	LAMP2: BS2
Clinical Genetics, Academic Medical Center	RCV000037404	SCV001926038	benign	not specified		no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001725947	SCV001963081	likely benign	not provided		no assertion criteria provided	clinical testing