ClinVar Miner

Submissions for variant NM_020366.4(RPGRIP1):c.1611+27G>A

dbSNP: rs1594203796
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV001005013 SCV001164575 likely pathogenic Leber congenital amaurosis 6 2018-12-03 criteria provided, single submitter research The heterozygous c.1611+27G>A variant in RPGRIP1 was identified by our study, in the compound heterozygous state, along with a pathogenic variant, in two siblings with Leber congenital amaurosis (PMID: 30072743). The c.1611+27G>A variant in RPGRIP1 has not been previously reported in individuals with Leber congenital amaurosis and was absent from large population studies. In vitro functional studies provide some evidence that the c.1611+27G>A variant may impact protein function (PMID: 30072743). However, these types of assays may not accurately represent biological function. This variant is located in the 5' splice region. Loss of function of the RPGRIP1 gene is an established disease mechanism in autosomal recessive Leber congenital amaurosis. The presence of this variant in combination with a reported pathogenic variant and in an individual with Leber congenital amaurosis increases the likelihood that the c.1611+27G>A variant is pathogenic. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic. ACMG/AMP Criteria applied: PM2, PS3, PM3 (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.