Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| SIB Swiss Institute of Bioinformatics | RCV000656353 | SCV000883198 | likely pathogenic | Hearing loss, autosomal recessive 57 | 2018-10-15 | criteria provided, single submitter | curation | This variant is interpreted as Likely Pathogenic, for Deafness, autosomal recessive, 57. The following ACMG Tag(s) were applied: PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PM1 => Located in a mutational hot spot and/or critical and well-established functional domain (e.g., active site of an enzyme) without benign variation (https://prosite.expasy.org/PDOC50106) (https://www.uniprot.org/uniprot/Q9H5P4). PP1 => Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease (https://www.ncbi.nlm.nih.gov/pubmed/26416264). |
| Invitae | RCV002536314 | SCV003439636 | likely pathogenic | not provided | 2022-07-19 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 545403). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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: "Not Available"; Align-GVGD: "Class C65"). This missense change has been observed in individual(s) with autosomal recessive deafness (PMID: 26416264). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs753034799, gnomAD 0.002%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 228 of the PDZD7 protein (p.Gly228Arg). |
| Prevention |
RCV003403513 | SCV004120689 | uncertain significance | PDZD7-related condition | 2023-06-20 | criteria provided, single submitter | clinical testing | The PDZD7 c.682G>A variant is predicted to result in the amino acid substitution p.Gly228Arg. This variant was reported in the homozygous state in three siblings with autosomal recessive hearing loss from an Iranian consanguineous pedigree (Booth. 2015. PubMed ID: 26416264) as well as one additional patient with hearing loss from Iran of unknown familial relationship (Table S4, Sloan-Heggen. 2015. PubMed ID: 26445815). This variant has also been reported in the homozygous state in a patient with an unspecified phenotype (Table S7, Stranneheim. 2021. PubMed ID: 33726816). This variant is reported in 0.0018% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/10-102782003-C-T). Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
| OMIM | RCV000656353 | SCV000778326 | pathogenic | Hearing loss, autosomal recessive 57 | 2018-06-01 | no assertion criteria provided | literature only |