ClinVar Miner

Submissions for variant NM_000180.4(GUCY2D):c.2595del (p.Lys866fs)

gnomAD frequency: 0.00003  dbSNP: rs1200134985
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001068218 SCV001233315 pathogenic Cone-rod dystrophy 6; Leber congenital amaurosis 1 2023-12-11 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys866Argfs*14) in the GUCY2D gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GUCY2D are known to be pathogenic (PMID: 10951519, 11328726). This variant is present in population databases (no rsID available, gnomAD 0.004%). This premature translational stop signal has been observed in individuals with Leber congenital amaurosis (PMID: 23035049, 29178642). ClinVar contains an entry for this variant (Variation ID: 861651). For these reasons, this variant has been classified as Pathogenic.
PreventionGenetics, part of Exact Sciences RCV003396718 SCV004104696 pathogenic GUCY2D-related disorder 2023-04-19 criteria provided, single submitter clinical testing The GUCY2D c.2595delG variant is predicted to result in a frameshift and premature protein termination (p.Leu865Leufs*15). This variant has been reported in the presumed and confirmed compound heterozygous state in individuals with Leber congenital amaurosis (Patient 10, Jacobson et al. 2013. PubMed ID: 23035049; Supplementary Table 1A and 3, Family ID0535, Thompson et al. 2017. PubMed ID: 29178642) and in the presumed compound heterozygous state in an individual with retinal dystrophy (Table S5, Subject ID 15014189, Taylor et al. 2017. PubMed ID: 28341476). This variant is reported in 0.0040% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/17-7918194-TG-T) and is interpreted as pathogenic on ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/861651/). Frameshift variants in GUCY2D are expected to be pathogenic. This variant is interpreted as pathogenic.
GenomeConnect - Invitae Patient Insights Network RCV001068218 SCV001749852 not provided Cone-rod dystrophy 6; Leber congenital amaurosis 1 no assertion provided phenotyping only Variant interpreted as Pathogenic and reported on 05-22-2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.

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