Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000293402 | SCV000394184 | uncertain significance | Fanconi anemia complementation group I | 2017-04-27 | criteria provided, single submitter | clinical testing | The FANCI c.849T>A (p.Tyr283Ter) variant is a stop-gained variant predicted to result in premature termination of the protein. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. The p.Tyr283Ter variant is reported at a frequency of 0.00001 in the European (non-Finnish) population of the Exome Aggregation Consortium. This frequency is based on one allele in a region of good coverage, so the variant is presumed to be rare. Due to the potential impact of stop-gained variants, and the lack of clarifying evidence, the p.Tyr283Ter variant is classified as a variant of unknown significance but suspicious for pathogenicity for Fanconi anemia. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002509364 | SCV002819662 | likely pathogenic | Fanconi anemia | 2022-12-19 | criteria provided, single submitter | clinical testing | Variant summary: FANCI c.849T>A (p.Tyr283X) 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 associated with Fanconi Anemia in HGMD. The variant allele was found at a frequency of 4e-06 in 251474 control chromosomes. To our knowledge, no occurrence of c.849T>A in individuals affected with Fanconi Anemia and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely pathogenic. |