Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002993785 | SCV003291842 | uncertain significance | Exostoses, multiple, type 2 | 2023-01-03 | criteria provided, single submitter | clinical testing | 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. 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. This variant has not been reported in the literature in individuals affected with EXT2-related conditions. This variant is present in population databases (rs778720458, gnomAD 0.03%). This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 286 of the EXT2 protein (p.Cys286Tyr). |
Laboratory of Molecular Epidemiology of Birth Defects, |
RCV003154267 | SCV003843683 | likely pathogenic | Ovarian cancer | 2022-01-01 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV003250683 | SCV003964271 | uncertain significance | Inborn genetic diseases | 2023-03-17 | criteria provided, single submitter | clinical testing | The c.857G>A (p.C286Y) alteration is located in exon 5 (coding exon 4) of the EXT2 gene. This alteration results from a G to A substitution at nucleotide position 857, causing the cysteine (C) at amino acid position 286 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |