ClinVar Miner

Submissions for variant NM_000355.4(TCN2):c.753+5G>A

gnomAD frequency: 0.00002  dbSNP: rs749028271
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001803581 SCV002049237 uncertain significance Transcobalamin II deficiency 2021-09-03 criteria provided, single submitter clinical testing The TCN2 c.753+5G>A variant (rs749028271), to our knowledge, is not reported in the medical literature or gene-specific databases. It is observed on only one allele in the Genome Aggregation Database, indicating it is not a common polymorphism. This is an intronic variant in a moderately conserved nucleotide, and computational analyses (Alamut v.2.11) predict that this variant may impact splicing by weakening the nearby canonical donor splice site. However, due to limited information, the clinical significance of the c.753+5G>A variant is uncertain at this time.
Labcorp Genetics (formerly Invitae), Labcorp RCV001803581 SCV003225723 uncertain significance Transcobalamin II deficiency 2022-08-21 criteria provided, single submitter clinical testing This sequence change falls in intron 5 of the TCN2 gene. It does not directly change the encoded amino acid sequence of the TCN2 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs749028271, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with TCN2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1330489). 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.