Submissions for variant NM_016938.5(EFEMP2):c.934A>G (p.Thr312Ala)

gnomAD frequency: 0.00085  dbSNP: rs148410446

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001088860	SCV000373177	uncertain significance	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae	RCV001088860	SCV000652073	likely benign	Cutis laxa, autosomal recessive, type 1B	2023-12-28	criteria provided, single submitter	clinical testing
Blueprint Genetics	RCV000788132	SCV000927142	uncertain significance	not provided	2017-02-03	criteria provided, single submitter	clinical testing
GeneDx	RCV000788132	SCV001793193	likely benign	not provided	2020-10-07	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001088860	SCV002049404	uncertain significance	Cutis laxa, autosomal recessive, type 1B	2020-10-25	criteria provided, single submitter	clinical testing	The EFEMP2 c.934A>G; p.Thr312Ala variant (rs148410446), to our knowledge, is not reported in the medical literature or gene specific databases. This variant is found in the general population with an overall allele frequency of 0.07 % (198 /282,392 alleles) in the Genome Aggregation Database. The threonine at codon 312 is highly conserved, but computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.38). Due to limited information, the clinical significance of the p.Thr312Ala variant is uncertain at this time.
Ambry Genetics	RCV002446555	SCV002682315	benign	Cardiovascular phenotype	2019-09-09	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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003485576	SCV004240555	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2023-01-17	criteria provided, single submitter	clinical testing