ClinVar Miner

Submissions for variant NM_032119.4(ADGRV1):c.17204+4A>G (rs376691612)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized 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,; 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 Clinical Services Laboratory,Illumina 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 2020-09-11 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, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs376691612, ExAC 0.01%). This variant has not been reported in the literature in individuals with ADGRV1-related conditions. ClinVar contains an entry for this variant (Variation ID: 504587). Nucleotide substitutions within 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 may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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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