Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000115349 | SCV000149258 | likely benign | not specified | 2017-11-28 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. |
Invitae | RCV000196582 | SCV000254260 | uncertain significance | Fanconi anemia | 2024-01-24 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 4 of the FANCC gene. It does not directly change the encoded amino acid sequence of the FANCC protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs368595927, gnomAD 0.02%). This variant has been observed in individual(s) with ovarian cancer (PMID: 30093976). ClinVar contains an entry for this variant (Variation ID: 127539). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Sema4, |
RCV000196582 | SCV002535102 | uncertain significance | Fanconi anemia | 2022-03-13 | criteria provided, single submitter | curation | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003477494 | SCV004218675 | uncertain significance | not provided | 2023-08-09 | criteria provided, single submitter | clinical testing | In the published literature, the variant has been reported in an individual with ovarian cancer (PMID: 30093976 (2018)). The frequency of this variant in the general population, 0.00018 (23/128838 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. Analysis of this variant using software algorithms for the prediction of the effect of nucleotide changes on FANCC mRNA splicing yielded predictions that this variant may result in the gain of a cryptic splice site without affecting the natural splice sites . Based on the available information, we are unable to determine the clinical significance of this variant. |