Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV002273283 | SCV002557040 | uncertain significance | Ritscher-Schinzel syndrome 2 | 2022-06-24 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3A. Following criteria are met: 0105 - The mechanism of disease for this gene is not clearly established. (I) 0109 - This gene is associated with X-linked recessive disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from glutamic acid to lysine. (I) 0253 - This variant is hemizygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0600 - Variant is located in the annotated CCDC22 domain (DECIPHER). (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0809 - Previous evidence of pathogenicity for this variant is inconclusive. This variant has been observed once in a large cohort study of hemizygous individuals with intellectual disability (PMID: 25644381). (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
| Greenwood Genetic Center Diagnostic Laboratories, |
RCV002273283 | SCV002568137 | likely pathogenic | Ritscher-Schinzel syndrome 2 | 2022-05-23 | criteria provided, single submitter | clinical testing | PS2, PM2, PP3 |
| Johns Hopkins Genomics, |
RCV002273283 | SCV002570303 | likely pathogenic | Ritscher-Schinzel syndrome 2 | 2022-02-12 | criteria provided, single submitter | clinical testing | This CCDC22 variant is absent from a large population dataset and has not been reported in ClinVar. In an X-chromosome resequencing study in 405 families with unresolved XLID, the c.622G>A variant was identified in a single male. However, detailed phenotypic information was not available for review. This variant was not identified in the patient's mother (JHG1794-2). Of three bioinformatics tools queried, two predict that the substitution would be damaging, while one predicts that it would be tolerated. The glutamate residue at this position is evolutionarily conserved across most mammalian species assessed. This variant is not predicted to affect normal exon 6 splicing, although this has not been confirmed experimentally to our knowledge. We consider this variant to be likely pathogenic. |