Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000228729 | SCV000283542 | pathogenic | Fanconi anemia | 2024-01-08 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Tyr359Profs*49) in the FANCA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FANCA are known to be pathogenic (PMID: 19367192). This variant is present in population databases (no rsID available, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with FANCA-related conditions (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 237032). For these reasons, this variant has been classified as Pathogenic. |
| Revvity Omics, |
RCV001782717 | SCV002022315 | pathogenic | Fanconi anemia complementation group A | 2019-06-17 | criteria provided, single submitter | clinical testing | |
| Sema4, |
RCV000228729 | SCV002534905 | pathogenic | Fanconi anemia | 2021-08-11 | criteria provided, single submitter | curation | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000228729 | SCV003845152 | likely pathogenic | Fanconi anemia | 2023-02-24 | criteria provided, single submitter | clinical testing | Variant summary: FANCA c.1074_1075delGT (p.Tyr359ProfsX49) 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 been classified as pathogenic by our laboratory. The variant was absent in 249030 control chromosomes (gnomAD). c.1074_1075delGT has been reported in the literature in individuals affected with Fanconi Anemia (example: Kimble_2018 and Nie_2020). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Baylor Genetics | RCV001782717 | SCV004041145 | pathogenic | Fanconi anemia complementation group A | 2023-06-21 | criteria provided, single submitter | clinical testing | |
| Natera, |
RCV000228729 | SCV002095070 | pathogenic | Fanconi anemia | 2021-06-03 | no assertion criteria provided | clinical testing |