ClinVar Miner

Submissions for variant NM_000203.5(IDUA):c.299+1G>T

gnomAD frequency: 0.00001  dbSNP: rs398123259
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000790824 SCV000227057 pathogenic not provided 2012-11-01 criteria provided, single submitter clinical testing
Counsyl RCV000175551 SCV000794881 likely pathogenic Hurler syndrome 2017-10-18 criteria provided, single submitter clinical testing
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV001249024 SCV001422946 likely pathogenic Mucopolysaccharidosis type 1 2020-01-13 criteria provided, single submitter curation The c.299+1G>T variant in IDUA has not been previously reported in individuals with mucopolysaccharidosis (MPS) but has been identified in 0.004% (1/27550) of Latino chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs398123259). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. This variant has also been reported in ClinVar (VariationID: 92639) as pathogenic by EGL Genetic Diagnostics and as likely pathogenic by Counsyl. This variant occurs in the invariant region (+/- 1/2) of the splice consensus sequence and is predicted to cause altered splicing leading to an abnormal or absent protein. Loss of function of the IDUA gene is an established disease mechanism in autosomal recessive MPS. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic. ACMG/AMP Criteria applied: PVS1_strong, PM2 (Richards 2015).

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.