ClinVar Miner

Submissions for variant NM_000180.4(GUCY2D):c.1956+1G>A

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
ClinGen Leber Congenital Amaurosis/early Onset Retinal Dystrophy Variant Curation Expert Panel, ClinGen RCV005054007 SCV005687746 pathogenic GUCY2D-related recessive retinopathy 2025-01-31 reviewed by expert panel curation The NM_000180.4(GUCY2D):c.1956+1G>A variant disrupts a canonical splice site in intron 9 and is predicted to lead to in-frame skipping of a critical exon (PVS1). This variant is present in gnomAD v.4.1.0 at an allele frequency of 6.202e-7, with 1 allele / 1612348 total alleles, which is lower than the ClinGen LCA/eoRD VCEP PM2_Supporting threshold of <0.0004 (PM2_Supporting). This variant has been reported in at least 1 proband with early-onset severe retinal dystrophy who was compound heterozygous with the NM_000180.4(GUCY2D):c.1672G>A (p.Asp558Asn) and NM_000180.4(GUCY2D):c.1245del (p.Phe415fs) variants confirmed in trans (1 point, PMID: 32865313), one of which was previously classified pathogenic by the ClinGen LCA/eoRD VCEP (1 1 point, PM3). The variant has been reported to segregate with childhood-onset severe retinal dystrophy through the proband plus 1 similarly affected relative, with the variant present in the compound heterozygous state (PMID: 32865313, PP1). In summary, this variant meets the criteria to be classified as pathogenic for GUCY2D-related recessive retinopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen LCA/eoRD VCEP: PVS1, PM2_Supporting, PM3, and PP1. (VCEP specifications version 1.0.0; date of approval 01/22/2025).
Fulgent Genetics, Fulgent Genetics RCV005022805 SCV005652771 likely pathogenic Choroidal dystrophy, central areolar, 1; Cone-rod dystrophy 6; Leber congenital amaurosis 1; Night blindness, congenital stationary, type1i 2024-04-23 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.