Submissions for variant NM_000393.5(COL5A2):c.2741C>T (p.Ala914Val)

gnomAD frequency: 0.00011  dbSNP: rs201486858

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000196083	SCV000249953	uncertain significance	not provided	2022-11-10	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics	RCV002310767	SCV000319649	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2021-12-13	criteria provided, single submitter	clinical testing	The p.A914V variant (also known as c.2741C>T), located in coding exon 41 of the COL5A2 gene, results from a C to T substitution at nucleotide position 2741. The alanine at codon 914 is replaced by valine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Illumina Laboratory Services, Illumina	RCV000396728	SCV000425636	uncertain significance	Ehlers-Danlos syndrome type 7A	2016-06-14	criteria provided, single submitter	clinical testing
Invitae	RCV002229086	SCV000547884	likely benign	Ehlers-Danlos syndrome, classic type, 1	2024-01-06	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000457016	SCV000895374	uncertain significance	Ehlers-Danlos syndrome, classic type	2018-10-31	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000196083	SCV001153242	uncertain significance	not provided	2019-03-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001143727	SCV001304276	likely benign	Ehlers-Danlos syndrome, classic type, 2	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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.