Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000523348 | SCV000618803 | likely pathogenic | not provided | 2018-12-31 | criteria provided, single submitter | clinical testing | The c.1776+1G>A variant in the FANCA gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This splice site variant destroys the canonical splice donor site in intron 19. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. The c.1776+1G>A variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret c.1776+1G>A as a likely pathogenic variant. |
Invitae | RCV000685268 | SCV000812744 | likely pathogenic | Fanconi anemia | 2022-11-11 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 450248). Disruption of this splice site has been observed in individual(s) with Fanconi anemia (PMID: 29098742). This variant is present in population databases (rs756140957, gnomAD 0.006%). This sequence change affects a donor splice site in intron 19 of the FANCA gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in FANCA are known to be pathogenic (PMID: 19367192). |
Baylor Genetics | RCV003464113 | SCV004196054 | pathogenic | Fanconi anemia complementation group A | 2023-08-19 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000523348 | SCV004221932 | pathogenic | not provided | 2023-08-29 | criteria provided, single submitter | clinical testing | The FANCA c.1776+1G>A variant disrupts a canonical splice-donor site and interferes with normal FANCA mRNA splicing. This variant has been reported in the published literature in an affected family with Fanconi anemia (PMID: 29098742 (2018)). The frequency of this variant in the general population, 0.000008 (2/251462 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is consistent with pathogenicity. Based on the available information, this variant is classified as pathogenic. |