ClinVar Miner

Submissions for variant NM_000093.5(COL5A1):c.4554+5G>A

gnomAD frequency: 0.00001  dbSNP: rs375489070
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000196959 SCV000249839 uncertain significance not provided 2017-01-20 criteria provided, single submitter clinical testing c.4554+5 G>A in intron 58 of the COL5A1 gene (NM_000093.3)IVS58+5 G>A : c.4554+5 G>A in intron 58 of the COL5A1 gene (NM_000093.3). The c.4554+5 G>A variant in the COL5A1 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. In silico splice prediction algorithms predict c.4554+5 G>A damages or destroys the natural donor site and may cause abnormal gene splicing. Other splice mutations in the COL5A1 gene have been reported in assocation with Ehlers Danlos syndrome. The c.4554+5 G>A variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project.Therefore, based on the currently available information, it is unclear whether c.4554+5 G>A is a pathogenic mutation or a rare benign variant.This variant was found in COL5A1,TAAD
Labcorp Genetics (formerly Invitae), Labcorp RCV002229056 SCV001201688 uncertain significance Ehlers-Danlos syndrome, classic type, 1 2024-11-21 criteria provided, single submitter clinical testing This sequence change falls in intron 58 of the COL5A1 gene. It does not directly change the encoded amino acid sequence of the COL5A1 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs375489070, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with COL5A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 212982). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV002336522 SCV002637252 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2019-04-04 criteria provided, single submitter clinical testing The c.4554+5G>A intronic variant results from a G to A substitution 5 nucleotides after coding exon 58 in the COL5A1 gene. This nucleotide position is well conserved in available vertebrate species; however, adenine is the reference nucleotide in other vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to weaken the efficiency of the native splice donor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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