Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| 3billion | RCV002251149 | SCV002521602 | pathogenic | Cardiac-urogenital syndrome | 2022-05-22 | criteria provided, single submitter | clinical testing | The variant is not observed in the gnomAD v2.1.1 dataset. Frameshift: predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported to be associated with MYRF- related disorder (PMID: 30985895). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. |
| Gene |
RCV002300655 | SCV002587970 | pathogenic | not provided | 2022-04-21 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 31633846, 30985895, 31266062) |
| Victorian Clinical Genetics Services, |
RCV002251149 | SCV002768328 | pathogenic | Cardiac-urogenital syndrome | 2022-02-02 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with cardiac-urogenital syndrome (MIM#618280). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0115 - Variants in this gene are known to have variable expressivity. Variants in this gene have been associated with a range of phenotypes from syndromic presentations of congenital diaphragmatic hernia, congenital heart disease, and genitourinary abnormalities to isolated nanophthalmos. (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0701 - Other NMD predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity (ClinVar). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been reported as de novo in an individual with nanophthalmos, in monozygotic twins with 46,XX disorders of sex development and in a fetus with coarctation of the aorta and pulmonary sequestration (PMID: 31266062, PMID: 30985895, PMID: 31633846). (SP) 1203 - This variant has been shown to be de novo in the proband (parental status confirmed) (by trio analysis). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
| Center for Genomic Medicine, |
RCV002251149 | SCV004808100 | uncertain significance | Cardiac-urogenital syndrome | 2024-03-29 | criteria provided, single submitter | clinical testing |