Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002238653 | SCV002511842 | likely pathogenic | Brittle cornea syndrome 2 | 2022-04-20 | criteria provided, single submitter | clinical testing | Variant summary: PRDM5 c.1785_1786delTA (p.His595GlnfsX14) results in a premature termination codon within the last exon, predicted to cause a truncation of the encoded protein, which is a commonly known mechanism for disease. This truncation is expected to abolish the last 22 amino acids and eliminate the majority of the most C-terminal zinc finger domain of the protein. The variant was absent in 250858 control chromosomes (gnomAD). To our knowledge, no occurrence of c.1785_1786delTA in individuals affected with Brittle Cornea Syndrome 2 and no experimental evidence demonstrating its impact on protein function have been reported. Nevertheless, other truncations within the last exon of PRDM5 have been reported in patients affected with Brittle Cornea Syndrome. Specifically, a truncation upstream of the variant (c.1768C>T, p.Arg590X) was reported in multiple homozygous affected individuals from one family (PMID: 21664999), while a truncation downstream of the variant (c.1858delC, p.His620ThrfsX8) has also been reported in one homozygous affected individual (PMID: 33739556). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |