Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000597354 | SCV000702021 | uncertain significance | not provided | 2016-09-30 | criteria provided, single submitter | clinical testing | |
Laboratory for Molecular Medicine, |
RCV000826006 | SCV000967494 | uncertain significance | not specified | 2019-02-28 | criteria provided, single submitter | clinical testing | The c.3122+3A>G variant in PCDH15 has not been previously reported in individuals with hearing loss but has been identified in 2/129002 European chromosomes by gnomAD (http://gnomad.broadinstitute.org). This variant is located in the 5' splice region. Computational tools do not predict a splicing impact, though this information is not predictive enough to rule out pathogenicity. In summary, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM2, BP4. |
Labcorp Genetics |
RCV000597354 | SCV003466413 | uncertain significance | not provided | 2022-06-25 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 23 of the PCDH15 gene. It does not directly change the encoded amino acid sequence of the PCDH15 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs373365331, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with PCDH15-related conditions. ClinVar contains an entry for this variant (Variation ID: 497490). 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 may disrupt the consensus 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. |
Gene |
RCV000597354 | SCV005419948 | uncertain significance | not provided | 2024-05-30 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on splicing; Has not been previously published as pathogenic or benign to our knowledge |
Natera, |
RCV001834865 | SCV002093001 | uncertain significance | Usher syndrome type 1F | 2020-11-11 | no assertion criteria provided | clinical testing |