Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Rady Children's Institute for Genomic Medicine, |
RCV001267672 | SCV001445905 | pathogenic | Nemaline myopathy 2 | 2019-05-15 | criteria provided, single submitter | clinical testing | This variant affects the canonical splice donor site of intron 73 and is therefore predicted to interfere with splicing and result in loss of normal protein function. This variant has not been previously reported or functionally characterized in the literature to our knowledge. A different variant at the same position (c.10872+1G>T) has been reported in the homozygous state in a patient with fetal akinesia (PMID: 28336317). Multiple splice prediction tools suggest this variant is likely to interfere with normal splicing. Based on the available evidence, the c.10872+1G>A variant is classified as a Pathogenic. |
| Invitae | RCV001267672 | SCV004279013 | pathogenic | Nemaline myopathy 2 | 2023-05-31 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 986357). Disruption of this splice site has been observed in individual(s) with congenital nemaline myopathy and/or fetal akinesia deformation sequence/lethal multiple pterygium syndrome (PMID: 25740301, 28336317). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 73 of the NEB 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 NEB are known to be pathogenic (PMID: 25205138). |