Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Baylor Genetics | RCV003460049 | SCV004192820 | uncertain significance | Exostoses, multiple, type 2 | 2023-07-28 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004621800 | SCV005120123 | uncertain significance | Inborn genetic diseases | 2024-04-15 | criteria provided, single submitter | clinical testing | The c.1582G>A (p.E528K) alteration is located in exon 10 (coding exon 9) of the EXT2 gene. This alteration results from a G to A substitution at nucleotide position 1582, causing the glutamic acid (E) at amino acid position 528 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003460049 | SCV005823303 | uncertain significance | Exostoses, multiple, type 2 | 2024-04-03 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 528 of the EXT2 protein (p.Glu528Lys). This variant is present in population databases (rs761890554, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with EXT2-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt EXT2 protein function with a positive predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |