Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000608513 | SCV000711063 | uncertain significance | not specified | 2016-06-07 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Pathogenic. The c.17204+4A> G variant in GPR98 has been previously reported by our laboratory in one individ ual with hearing loss, but a variant affecting the remaining copy of the gene ha s not been identified. A different variant in this splice region (c.17204+4_1720 4+7del) has been previously reported in the compound heterozygous or homozygous state in two individuals with Usher syndrome (Besnard 2012, Garcia-Garcia 2013). This variant has also been identified in 8/66576 of European chromosomes by th e Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; rs37669161 2); however, its frequency is not high enough to rule out a pathogenic role. Thi s variant is located in the 5' splice region. Computational tools suggest an imp act to splicing. However, this information is not predictive enough to determine pathogenicity. In summary, while there is some suspicion for a pathogenic role, the clinical significance of the c.17204+4A>G is uncertain. |
Illumina Laboratory Services, |
RCV001153447 | SCV001314733 | uncertain significance | Usher syndrome type 2C | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
Invitae | RCV001298601 | SCV001487662 | uncertain significance | not provided | 2022-08-23 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 79 of the ADGRV1 gene. It does not directly change the encoded amino acid sequence of the ADGRV1 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs376691612, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with ADGRV1-related conditions. ClinVar contains an entry for this variant (Variation ID: 504587). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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. |