ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.9259-14A>C

gnomAD frequency: 0.00001  dbSNP: rs561590242
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000221196 SCV000269953 benign not specified 2015-02-20 criteria provided, single submitter clinical testing c.9259-14A>C in intron 46 of USH2A: This variant is not expected to have clinica l significance because it has been identified in 0.7% (109/16498) of South Asia n chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstit ute.org; dbSNP rs561590242), and a cytosine "C" at this position does not diverg e from the 3' splice site consensus sequence.
Invitae RCV001509798 SCV001716673 benign not provided 2024-01-29 criteria provided, single submitter clinical testing
GeneDx RCV001509798 SCV002031131 likely benign not provided 2021-06-05 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000221196 SCV002819548 likely benign not specified 2022-12-14 criteria provided, single submitter clinical testing Variant summary: USH2A c.9259-14A>C alters a non-conserved nucleotide located near a canonical splice site and therefore could affect mRNA splicing. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00075 in 251180 control chromosomes in the gnomAD database, including 1 homozygote. This frequency is not significantly higher than estimated for a pathogenic variant in USH2A causing Usher Syndrome (0.00075 vs 0.011), however the presence of a homozygous individual is supportive of the benign nature of the variant. To our knowledge, no occurrence of c.9259-14A>C in individuals affected with Usher Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
Genome-Nilou Lab RCV003445698 SCV004172041 benign Retinitis pigmentosa 39 2023-04-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003445697 SCV004172042 benign Usher syndrome type 2A 2023-04-11 criteria provided, single submitter clinical testing

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.