ClinVar Miner

Submissions for variant NM_000487.6(ARSA):c.302dup (p.Leu102fs)

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
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001193047 SCV001361596 pathogenic Metachromatic leukodystrophy 2019-10-03 criteria provided, single submitter clinical testing Variant summary: ARSA c.302dupG (p.Leu102ProfsX32) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 3.6e-05 in 195014 control chromosomes (gnomAD). c.302dupG has been reported in the literature in multiple individuals affected with Metachromatic Leukodystrophy (Perkins_2005, Lugowska_2009, Lugowska_2010, Dali_2015, Chen_2018). These data indicate that the variant is very likely to be associated with disease. Experimental evidence evaluating an impact on protein function through expression of the variant in CHO cells, determined a negligible level of ARSA activity (0.3% of the activity in wild-type CHO cells) (Lugowska_2009). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV001193047 SCV001384115 pathogenic Metachromatic leukodystrophy 2020-06-01 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu102Profs*32) in the ARSA gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs761606317, ExAC 0.004%). This variant has been observed in combination with another ARSA variant in an individual affected with metachromatic leukodystrophy (PMID: 19021637). Loss-of-function variants in ARSA are known to be pathogenic (PMID: 8962139, 10477432). For these reasons, this variant has been classified as Pathogenic.

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.