Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000633255 | SCV000754472 | likely pathogenic | Werner syndrome | 2017-10-23 | criteria provided, single submitter | clinical testing | Nucleotide substitutions within the consensus splice site are relatively common causes of aberrant splicing (PMID: 17576681, 9536098), and loss-of-function variants in WRN are known to be pathogenic (PMID: 16673358). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site and result in an absent or disrupted protein product, but this prediction has not been confirmed by published transcriptional studies. This sequence change removes the last nucleotide of exon 7 and the first 3 nucleotides of intron 7 of the WRN gene. It does not directly change the donor splice site in intron 7 of the WRN gene, but it does affect several nucleotides within 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. This variant has not been reported in the literature in individuals with WRN-related disease. This variant is not present in population databases (ExAC no frequency). |