Submissions for variant NM_000393.5(COL5A2):c.1716+5G>A

dbSNP: rs863223504

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000199203	SCV000250009	uncertain significance	not provided	2014-12-31	criteria provided, single submitter	clinical testing	TAAD is a genetically heterogeneous disorder characterized by aortic dilatation, aneurysms, dissections and/or aneurysms of other major arteries. Approximately 4% of patients with autosomal dominant Ehlers-Danlos syndrome, classic type, have been reported to have a mutation in the COL5A2 gene (Malfait F et al., 2011). c.1716+5 G>A in intron 25 of the COL5A2 gene (NM_000393.3) A variant of unknown significance has been identified in the COL5A2 gene. The c.1716+5 G>A variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. In silico splice prediction programs predict c.1716+5 G>A results in decreased efficiency of the natural splice donor site of intron 25, which may lead to either an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. Other splice site mutations in the COL5A2 gene have been reported in association with Ehlers-Danlos syndrome. Additionally, the c.1716+5 G>A variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. This variant was found in TAADV2-1.