Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001806810 | SCV002051312 | likely pathogenic | Brittle cornea syndrome 1 | 2021-12-21 | criteria provided, single submitter | clinical testing | Variant summary: ZNF469 c.10707C>A (p.Cys3569X), located in the last exon (exon 3) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have not been classified as pathogenic by our laboratory, however, at-least one other frameshifting loss of function variant (c.10751delC, p.Pro3584Glnfs*136) has been reported with a phenotype of Brittle Cornea syndrome in the HGMD database. The variant allele was found at a frequency of 1.3e-05 in 152694 control chromosomes. To our knowledge, no occurrence of c.10707C>A in individuals affected with Brittle Cornea Syndrome 1 and no experimental evidence demonstrating its impact on protein function have been reported. 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. |