Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV005239933 | SCV005887948 | pathogenic | Joubert syndrome and related disorders | 2025-01-07 | criteria provided, single submitter | clinical testing | Variant summary: The variant involves the deletion of exons 1-20 of the NPHP1 gene. A presumed nomenclature of c.(?_-46)_(*444_?)del has been designated for the purposes of this classification. This deletion includes the entire coding sequence of the gene. As the exact proximal and distal breakpoints are unknown, it may extend beyond the annotated region of the gene to include other flanking genes. A similar copy number variant encompassing all of the NPHP1 coding sequence was found at a frequency of 0.0018 in 21694 control chromosomes. The observed variant frequency is approximately 3.22 fold of the estimated maximal expected allele frequency for a pathogenic variant in NPHP1 causing Joubert Syndrome And Related Disorders phenotype (0.00056), however whole gene deletions are commonly reported among individuals with NPHP1-related conditions. c.(?_-46)_(*444_?)del has been reported in the literature in numerous individuals affected with Joubert Syndrome And Related Disorders (example, Cheema_2020). The following publication have been ascertained in the context of this evaluation (PMID: 33083013). ClinVar contains an entry for this variant (Variation ID: 237627). Based on the evidence outlined above, the variant was classified as pathogenic. |