ClinVar Miner

Submissions for variant NM_004937.3(CTNS):c.853-2A>G

dbSNP: rs1475322504
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
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 RCV000588528 SCV000698527 pathogenic Cystinosis 2017-02-02 criteria provided, single submitter clinical testing Variant summary: The CTNS c.853-2A>G variant involves the alteration of a conserved intronic nucleotide. One in silico tool predicts a damaging outcome for this variant. 4/4 splice prediction tools predict the complete loss of a canonical 5' splice acceptor site. These predictions have been confired by functional studies showing patient RNA having a transcript that contains the first 41bp of IVS10 and a deletion of the first 26 bp of exon11. This variant is absent in 118932 control chromosomes but has been reported in a severely affected proband in the literature. Taken together, this variant is classified as pathogenic.
Counsyl RCV000666666 SCV000790995 likely pathogenic Nephropathic cystinosis 2017-04-18 criteria provided, single submitter clinical testing
Baylor Genetics RCV000666666 SCV004212951 pathogenic Nephropathic cystinosis 2023-09-17 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV005091543 SCV005641937 likely pathogenic Ocular cystinosis; Juvenile nephropathic cystinosis; Nephropathic cystinosis 2024-04-06 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV005223021 SCV005863179 pathogenic Ocular cystinosis; Juvenile nephropathic cystinosis; Inborn genetic diseases 2024-08-31 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 10 of the CTNS gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CTNS are known to be pathogenic (PMID: 9537412, 27102039). This variant is present in population databases (no rsID available, gnomAD 0.0009%). Disruption of this splice site has been observed in individual(s) with cystinosis (PMID: 12442267, 29421779). This variant is also known as c.1192-2A>G. ClinVar contains an entry for this variant (Variation ID: 496277). Studies have shown that disruption of this splice site is associated with inconclusive levels of altered splicing (PMID: 12442267). 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.