Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001345721 | SCV001539860 | uncertain significance | Focal segmental glomerulosclerosis 5; Charcot-Marie-Tooth disease dominant intermediate E | 2020-03-03 | criteria provided, single submitter | clinical testing | 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. The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in INF2 cause disease. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with INF2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 20 of the INF2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. |
| Ambry Genetics | RCV002445199 | SCV002753965 | uncertain significance | Inborn genetic diseases | 2020-02-13 | criteria provided, single submitter | clinical testing | The c.3040+2T>C intronic variant results from a T to C substitution two nucleotides after coding exon 19 in the INF2 gene. This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice donor site; however, direct evidence is unavailable. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. However, loss of function of INF2 has not been clearly established as a mechanism of disease. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Bioscientia Institut fuer Medizinische Diagnostik Gmb |
RCV001029884 | SCV001192675 | uncertain significance | Focal segmental glomerulosclerosis 5 | 2019-03-14 | no assertion criteria provided | clinical testing |