Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000760454 | SCV000890340 | pathogenic | not provided | 2018-06-12 | criteria provided, single submitter | clinical testing | The E103X variant in the MESP2 gene has been reported previously as a founder variant in the Puerto Rican population and has been observed frequently in the homozygous and compound heterozygous states in individuals with spondylothoracic dysostosis (STD) (Cornier et al., 2008). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The E103X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). We interpret E103X as a pathogenic variant. |
Invitae | RCV000760454 | SCV000947457 | pathogenic | not provided | 2024-01-31 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu103*) in the MESP2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MESP2 are known to be pathogenic (PMID: 9242490, 18485326). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with spondylocostal dysostosis (PMID: 18485326). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 5184). For these reasons, this variant has been classified as Pathogenic. |
OMIM | RCV000005493 | SCV000025675 | pathogenic | Spondylocostal dysostosis 2, autosomal recessive | 2008-06-01 | no assertion criteria provided | literature only | |
Gene |
RCV000005493 | SCV000055731 | pathologic | Spondylocostal dysostosis 2, autosomal recessive | 2010-08-05 | no assertion criteria provided | curation | Converted during submission to Pathogenic. |
Natera, |
RCV000005493 | SCV001454605 | pathogenic | Spondylocostal dysostosis 2, autosomal recessive | 2020-09-16 | no assertion criteria provided | clinical testing |