Submissions for variant NM_000393.5(COL5A2):c.3794A>G (p.Asp1265Gly)

gnomAD frequency: 0.00006  dbSNP: rs200325397

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000356709	SCV000425615	uncertain significance	Ehlers-Danlos syndrome type 7A	2016-06-14	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002313005	SCV000738743	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2022-11-03	criteria provided, single submitter	clinical testing	The p.D1265G variant (also known as c.3794A>G), located in coding exon 51 of the COL5A2 gene, results from an A to G substitution at nucleotide position 3794. The aspartic acid at codon 1265 is replaced by glycine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae	RCV002229381	SCV000933209	likely benign	Ehlers-Danlos syndrome, classic type, 1	2024-01-04	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001139304	SCV001299436	likely benign	Ehlers-Danlos syndrome, classic type, 2	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.
GeneDx	RCV001569254	SCV001793294	uncertain significance	not provided	2023-03-22	criteria provided, single submitter	clinical testing	Reported in a patient with Marfan syndrome in the published literature, however this individual also harbored an additional cardiogenetic variant (Hambly et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not located in the triple helical region, where the majority of pathogenic missense variants occur (Symoens et al., 2012; HGMD); This variant is associated with the following publications: (PMID: 22696272)
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001139304	SCV002047769	uncertain significance	Ehlers-Danlos syndrome, classic type, 2	2020-10-21	criteria provided, single submitter	clinical testing	The COL5A2 c.3794A>G; p.Asp1265Gly variant (rs200325397), to our knowledge, has not been reported in the medical literature; however, this variant is listed in the ClinVar database (Variation ID: 180305). This variant is found in the general population with an overall allele frequency of 0.007% (19/282,758 alleles) in the Genome Aggregation Database. The aspartic acid at codon 1265 is highly conserved, and computational analyses predict that this variant is deleterious (REVEL: 0.726). However, based on the available information, the clinical significance of this variant is uncertain.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002277314	SCV002565833	uncertain significance	Ehlers-Danlos syndrome	2021-06-14	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001569254	SCV004698681	uncertain significance	not provided	2023-12-01	criteria provided, single submitter	clinical testing
Blueprint Genetics	RCV000157152	SCV000206875	uncertain significance	Marfan syndrome	2014-05-09	no assertion criteria provided	clinical testing