Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001360598 | SCV001556523 | uncertain significance | Cone-rod dystrophy 6; Leber congenital amaurosis 1 | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with asparagine at codon 279 of the GUCY2D protein (p.Asp279Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with Leber congenital amaurosis (PMID: 26047050). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). 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. |
| 3billion | RCV002250753 | SCV002521206 | likely pathogenic | Leber congenital amaurosis 1 | 2022-05-22 | criteria provided, single submitter | clinical testing | Different pathogenic amino acid change has been reported with supporting evidence at the same codon (PMID:31630094). In silico prediction tools and conservation analysis predicted that this variant was probably damaging to the protein structure/function (REVEL: 0.624>=0.6). It has been reported with an extremely low frequency in the gnomAD v2.1.1 (https://gnomad.broadinstitute.org/) dataset. Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline. |