Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000203795 | SCV000259618 | pathogenic | Fanconi anemia | 2024-01-15 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Cys1209Leufs*10) in the FANCI gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FANCI are known to be pathogenic (PMID: 17452773, 17460694). This variant is present in population databases (rs770318990, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with FANCI-related conditions. ClinVar contains an entry for this variant (Variation ID: 219634). For these reasons, this variant has been classified as Pathogenic. |
| Fulgent Genetics, |
RCV002478726 | SCV002782550 | pathogenic | Fanconi anemia complementation group I | 2022-05-04 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000203795 | SCV003929160 | likely pathogenic | Fanconi anemia | 2023-04-06 | criteria provided, single submitter | clinical testing | Variant summary: FANCI c.3626_3627delGT (p.Cys1209LeufsX10) 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 associated with Fancomi Anemia in HGMD. The variant allele was found at a frequency of 4e-06 in 251472 control chromosomes. c.3626_3627delGT has been reported in the literature in families with hereditary breast and ovarian cancer (Tavera-Tapia_2017, Quezada-Urban_2018, etc.). 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 (n=2). Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Baylor Genetics | RCV002478726 | SCV004199193 | likely pathogenic | Fanconi anemia complementation group I | 2023-10-17 | criteria provided, single submitter | clinical testing |