Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000816054 | SCV000956543 | likely pathogenic | Fanconi anemia | 2023-03-02 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This sequence change affects a donor splice site in intron 20 of the FANCM 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 FANCM are known to be pathogenic (PMID: 29895858, 30075111). This variant is present in population databases (rs754297345, gnomAD 0.005%). Disruption of this splice site has been observed in individual(s) with astrocytoma, ovarian cancer, and/or pancreatic adenocarcinoma (PMID: 28881617, 29625052, 31970404). ClinVar contains an entry for this variant (Variation ID: 659108). 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. |
Gene |
RCV003228996 | SCV003926135 | likely pathogenic | not provided | 2023-05-08 | criteria provided, single submitter | clinical testing | Canonical splice site variant predicted to result in an in-frame loss of the adjacent exon in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Observed in an individual with ovarian cancer and in an individual with astrocytoma (Dicks et al., 2017; Muskens et al., 2020); This variant is associated with the following publications: (PMID: 29625052, 28881617, 31970404, 33804961) |