Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001387516 | SCV001588175 | pathogenic | not provided | 2017-09-07 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with FRAS1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Arg2269*) in the FRAS1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FRAS1 are known to be pathogenic (PMID: 12766769, 18671281). For these reasons, this variant has been classified as Pathogenic. |
| Revvity Omics, |
RCV001780361 | SCV002023756 | pathogenic | Fraser syndrome 1 | 2021-02-15 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001780361 | SCV002074393 | pathogenic | Fraser syndrome 1 | 2022-01-21 | criteria provided, single submitter | clinical testing | Variant summary: FRAS1 c.6805C>T (p.Arg2269X) 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 but reported in the HGMD database. The variant allele was found at a frequency of 4e-06 in 248854 control chromosomes. c.6805C>T has been reported in the literature in at-least one individual affected with Fraser syndrome (Cryptophthalmos Syndrome)(example, Midro_2020). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |