Submissions for variant NM_016938.5(EFEMP2):c.368-4G>A

gnomAD frequency: 0.00223  dbSNP: rs111550973

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000219848	SCV000269074	benign	not specified	2013-02-21	criteria provided, single submitter	clinical testing	368-4G>A in intron 4 of EFEMP2: This variant is not expected to have clinical si gnificance because it is not located within the conserved splice consensus seque nce. It has been identified in 0.3% (30/8592) of European American chromosomes f rom a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.wash ington.edu/EVS; dbSNP rs111550973).
GeneDx	RCV000589251	SCV000528069	likely benign	not provided	2021-02-15	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 26017485)
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000547436	SCV000603422	benign	Cutis laxa, autosomal recessive, type 1B	2024-10-28	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000547436	SCV000652061	benign	Cutis laxa, autosomal recessive, type 1B	2025-02-03	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589251	SCV000699429	benign	not provided	2017-07-14	criteria provided, single submitter	clinical testing	Variant summary: The EFEMP2 c.368-4G>A variant involves the alteration of a non-conserved intronic nucleotide. Mutation taster predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. This variant was found in 219/121494 control chromosomes (1 homozygote) including ExAC at a frequency of 0.0018026, which is approximately 16 times the estimated maximal expected allele frequency of a pathogenic EFEMP2 variant (0.0001118), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories (via ClinVar) have classified this variant as benign. To our knowledge, the variant of interest has not been reported in affected individuals in literature. Taken together, this variant is classified as benign.
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000547436	SCV000744895	likely benign	Cutis laxa, autosomal recessive, type 1B	2015-07-22	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000589251	SCV001148331	likely benign	not provided	2024-04-01	criteria provided, single submitter	clinical testing	EFEMP2: BP4
Illumina Laboratory Services, Illumina	RCV000547436	SCV001266214	likely benign	Cutis laxa, autosomal recessive, type 1B	2018-01-12	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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Ambry Genetics	RCV002453758	SCV002614245	benign	Cardiovascular phenotype	2019-10-21	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, 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.
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000547436	SCV000745738	likely benign	Cutis laxa, autosomal recessive, type 1B	2014-02-04	no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000589251	SCV001799981	likely benign	not provided		no assertion criteria provided	clinical testing