Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000497711 | SCV000589792 | likely pathogenic | not provided | 2016-03-07 | criteria provided, single submitter | clinical testing | The c.2431+5 G>A variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.2431+5 G>A variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Several in-silico splice prediction models predict that c.2431+5 G>A destroys the natural donor site which may lead to abnormal gene splicing. However, in the absence of RNA/functional studies, the actual effect of this sequence change in this individual is unknown. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded. |
Invitae | RCV001234704 | SCV001407362 | pathogenic | Spastic paraplegia | 2019-11-11 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Nucleotide substitutions within 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 may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has been observed in individual(s) with L1CAM-related conditions (Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 432107). This variant is not present in population databases (ExAC no frequency). This sequence change falls in intron 18 of the L1CAM gene. It does not directly change the encoded amino acid sequence of the L1CAM protein, but it affects a nucleotide within the consensus splice site of the intron. |