ClinVar Miner

Submissions for variant NM_000180.4(GUCY2D):c.295G>A (p.Ala99Thr)

gnomAD frequency: 0.00001  dbSNP: rs1304984076
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001297954 SCV001486994 uncertain significance Cone-rod dystrophy 6; Leber congenital amaurosis 1 2021-08-27 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 99 of the GUCY2D protein (p.Ala99Thr). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and threonine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has not been reported in the literature in individuals affected with GUCY2D-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.

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