Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000254724 | SCV000321619 | pathogenic | not provided | 2021-11-12 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 17041877, 16283885, 33726816, 28849184) |
Invitae | RCV000552959 | SCV000640992 | pathogenic | Exostoses, multiple, type 2 | 2024-01-09 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln313*) in the EXT2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in EXT2 are known to be pathogenic (PMID: 10679937, 19810120). This variant is present in population databases (rs763718818, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with multiple osteochondromas (PMID: 16283885, 28849184). ClinVar contains an entry for this variant (Variation ID: 265134). For these reasons, this variant has been classified as Pathogenic. |
Prevention |
RCV003930032 | SCV004738237 | pathogenic | EXT2-related disorder | 2023-11-03 | criteria provided, single submitter | clinical testing | The EXT2 c.937C>T variant is predicted to result in premature protein termination (p.Gln313*). This variant has been reported in individuals with multiple osteochondromas (Wuyts et al. 2005. PubMed ID: 16283885; Table S1, Jennes et al. 2009. PubMed ID: 19810120; described as c.1036C>T/p.Gln346X in Xu et al. 2017. PubMed ID: 28849184). This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/11-44146532-C-T). Nonsense variants in EXT2 are expected to be pathogenic. This variant is interpreted as pathogenic. |