Submissions for variant NM_002294.3(LAMP2):c.741+11C>T

gnomAD frequency: 0.00024  dbSNP: rs149155417

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000037426	SCV000061083	benign	not specified	2012-11-20	criteria provided, single submitter	clinical testing	741+11C>T in intron 5 of LAMP2: This variant is not expected to have clinical si gnificance because it has been identified in 2.1% (9/428) Asian chromosomes from a broad population by the 1000 Genomes project (dbSNP rs149155417).
Illumina Laboratory Services, Illumina	RCV001168183	SCV001330758	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000037426	SCV001363684	benign	not specified	2019-11-04	criteria provided, single submitter	clinical testing	Variant summary: LAMP2 c.741+11C>T alters a nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.001 in 182348 control chromosomes (gnomAD). The observed variant frequency is approximately 81 fold of the estimated maximal expected allele frequency for a pathogenic variant in LAMP2 causing Cardiomyopathy phenotype (1.3e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.741+11C>T in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as benign.
GeneDx	RCV001711121	SCV001939633	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Invitae	RCV001168183	SCV002475093	benign	Danon disease	2024-01-28	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001711121	SCV001978111	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000037426	SCV001979134	benign	not specified		no assertion criteria provided	clinical testing