Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000689733 | SCV000817399 | uncertain significance | Joubert syndrome 25 | 2022-10-24 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 913 of the CEP104 protein (p.Gly913Arg). This variant is present in population databases (rs201733773, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with CEP104-related conditions. ClinVar contains an entry for this variant (Variation ID: 569168). 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: "Benign"; Align-GVGD: "Class C0"). 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. |
Ambry Genetics | RCV002547143 | SCV003664496 | uncertain significance | Inborn genetic diseases | 2021-07-29 | criteria provided, single submitter | clinical testing | The c.2737G>A (p.G913R) alteration is located in exon 22 (coding exon 21) of the CEP104 gene. This alteration results from a G to A substitution at nucleotide position 2737, causing the glycine (G) at amino acid position 913 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Clinical Genomics Program, |
RCV000689733 | SCV004228237 | uncertain significance | Joubert syndrome 25 | 2021-05-27 | criteria provided, single submitter | clinical testing | The p.Gly913Arg variant in the CEP104 gene has not been previously reported in association with disease. This variant was identified in trans with the c.2662+10A>T variant in this individual. The p.Gly913Arg variant has been identified in 62/281,042 chromosomes by the Genome Aggregation Database (http://gnomad.broadinstitute.org/). Although this variant has been seen in the general population, it has not been observed at a high enough frequency to rule out pathogenicity. Computational tools predict that this variant does not impact protein function; however, the accuracy of in silico algorithms is limited. These data were assessed using the ACMG/AMP variant interpretation guidelines. In summary, the significance of the p.Gly913Arg variant is uncertain. Additional information is needed to resolve the significance of this variant. [ACMG evidence codes used: BP4] |