Submissions for variant NM_016938.5(EFEMP2):c.277G>A (p.Gly93Ser)

gnomAD frequency: 0.00344  dbSNP: rs2234462

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CeGaT Center for Human Genetics Tuebingen	RCV000488325	SCV000574890	likely benign	not provided	2023-12-01	criteria provided, single submitter	clinical testing	EFEMP2: BP4, BS1
Invitae	RCV000535424	SCV000652054	benign	Cutis laxa, autosomal recessive, type 1B	2024-01-31	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000488325	SCV000699428	benign	not provided	2017-07-14	criteria provided, single submitter	clinical testing	Variant summary: The EFEMP2 c.277G>A (p.Gly93Ser) variant involves the alteration of a non-conserved nucleotide. 2/3 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 354/122264 control chromosomes including ExAC, predominantly observed in the European (Finnish) subpopulation at a frequency of 0.009828 (65/6614). This frequency is about 88 times the estimated maximal expected allele frequency of a pathogenic EFEMP2 variant (0.0001118), suggesting this is likely a benign polymorphism found primarily in the populations of European (Finnish) origin. This variant has been found in multiple familial abdominal aortic aneurysm without evidence of segregation (van de Luijtgaarden_2015) and was classified as likely benign by the authors. One diagnostic laboratory has classified uncertain significance without evidence to independently evaluate. Taken together, this variant is classified as benign.
GeneDx	RCV000488325	SCV000718335	benign	not provided	2018-11-30	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 26017485)
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000535424	SCV000744896	likely benign	Cutis laxa, autosomal recessive, type 1B	2017-05-31	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000535424	SCV001156848	benign	Cutis laxa, autosomal recessive, type 1B	2023-11-29	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000535424	SCV001266217	benign	Cutis laxa, autosomal recessive, type 1B	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Ambry Genetics	RCV002438189	SCV002751675	benign	Cardiovascular phenotype	2019-01-29	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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003485591	SCV004240551	benign	Familial thoracic aortic aneurysm and aortic dissection	2023-05-16	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000535424	SCV000745739	likely benign	Cutis laxa, autosomal recessive, type 1B	2014-02-04	no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000616268	SCV001927397	benign	not specified		no assertion criteria provided	clinical testing