Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001378519 | SCV001576103 | likely pathogenic | Fanconi anemia | 2024-01-04 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 26 of the FANCD2 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 FANCD2 are known to be pathogenic (PMID: 17436244). This variant is present in population databases (rs779552164, gnomAD 0.003%). Disruption of this splice site has been observed in individual(s) with prostate cancer (PMID: 29659569). ClinVar contains an entry for this variant (Variation ID: 1067299). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |
DASA | RCV002221627 | SCV002498802 | likely pathogenic | Fanconi anemia complementation group D2 | 2022-04-10 | criteria provided, single submitter | clinical testing | The c.2494+2T>C variant is located in a canonical splice-site, and it is not predicted the protein reading frame alteration, however, occur in a critical region and the variant disrupts ˃10% of the protein - PVS1_strong. This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant (PMID: 29659569) - PS4_supporting. The variant is present at low allele frequencies population databases (rs779552164 – gnomAD 0.00008072%; ABraOM no frequency - http://abraom.ib.usp.br) - PM2_supporting. In summary, the currently available evidence indicates that the variant is likely pathogenic |
Baylor Genetics | RCV002221627 | SCV004196764 | likely pathogenic | Fanconi anemia complementation group D2 | 2023-02-24 | criteria provided, single submitter | clinical testing |