Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001306871 | SCV001496256 | uncertain significance | Cone-rod dystrophy 6; Leber congenital amaurosis 1 | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with leucine at codon 711 of the GUCY2D protein (p.Pro711Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs765463082, ExAC 0.006%). This missense change has been observed in individuals with Lebercongenital amaurosis (PMID: 20683928, 23847139). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004690034 | SCV005184421 | likely pathogenic | Leber congenital amaurosis | 2024-05-31 | criteria provided, single submitter | clinical testing | Variant summary: GUCY2D c.2132C>T (p.Pro711Leu) results in a non-conservative amino acid change located in the Protein kinase domain (IPR000719) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 249576 control chromosomes. c.2132C>T has been reported in the literature in at-least three individuals affected with Leber Congenital Amaurosis (Coppieters_2010, Wang_2013, Xu_2020). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 20683928, 23847139, 31630094). ClinVar contains an entry for this variant (Variation ID: 974639). Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Laboratory of Genetics in Ophthalmology, |
RCV001250836 | SCV001426326 | likely pathogenic | Leber congenital amaurosis 1 | no assertion criteria provided | research |