Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001059704 | SCV001224342 | pathogenic | Exostoses, multiple, type 2 | 2024-04-02 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Val154Profs*115) 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 not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with hereditary multiple osteochondromas (PMID: 23262345, 24496678, 28922105). This variant is also known as c.455_458del. ClinVar contains an entry for this variant (Variation ID: 854619). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| Molecular Genetics, |
RCV001059704 | SCV004812847 | pathogenic | Exostoses, multiple, type 2 | 2023-08-01 | criteria provided, single submitter | clinical testing | This sequence change in EXT2 is a frameshift variant predicted to cause a premature stop codon, p.(Val154Profs*115), in biologically relevant exon 5/14 leading to nonsense-mediated decay in a gene in which loss-of-function is an established disease mechanism. This variant is absent from the population database gnomAD v2.1 and v3.1. This variant has been reported in at least three unrelated probands diagnosed with EXT2-related hereditary multiple exostoses (PMID: 23262345, 24496678, 28922105). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.6.1, this variant is classified as PATHOGENIC. Following criteria are met: PVS1, PM2_Supporting, PS4_Supporting. |