Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002014522 | SCV002230312 | pathogenic | Fanconi anemia | 2023-12-21 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln623*) in the FANCD2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FANCD2 are known to be pathogenic (PMID: 17436244). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This variant has not been reported in the literature in individuals affected with FANCD2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1449465). For these reasons, this variant has been classified as Pathogenic. |
| Fulgent Genetics, |
RCV002507683 | SCV002813024 | likely pathogenic | Fanconi anemia complementation group D2 | 2021-09-27 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002014522 | SCV003923232 | likely pathogenic | Fanconi anemia | 2023-03-23 | criteria provided, single submitter | clinical testing | Variant summary: FANCD2 c.1866_1867delinsAT (p.Gln623X) 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 in ClinVar and reported in association with Fanconi Anemia in HGMD. The variant allele was found at a frequency of 4e-06 in 251446 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1866_1867delinsAT in individuals affected with Fanconi Anemia and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014, and both laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |