Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003226636 | SCV003922522 | pathogenic | Fanconi anemia | 2023-03-22 | criteria provided, single submitter | clinical testing | Variant summary: The variant identified by MLPA or other technology involves the deletion of exons 1-3 in the FANCA gene, where exon 1 contains the translation initiation codon. The exact breakpoint at the 5' end of this variant is unknown and therefore this deletion might extend upstream of the assayed region of the gene. A presumed nomenclature of c.(?_-43)_(283+1_284-1)del has been designated for the purposes of this classification. Although exact breakpoints of this deletion are not known, it is expected to result in an absent or shortened protein product, a known mechanism of disease. The variant was absent in 21694 control chromosomes (gnomAD, structural variants dataset). The variant, c.(?_-43)_(283+1_284-1)del, has been reported in the literature in multiple compound heterozygous individuals affected with Fanconi Anemia (e.g. Castella_2011, Flynn_2014, Mori_2019, Toksoy_2020), who carried another (likely) pathogenic variant in trans. These data indicate that the variant is likely to be associated with disease. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014, and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |