EZHIP is a protein-coding gene on the X chromosome that plays a role in epigenetic regulation: it inhibits histone methyltransferases and interacts with the Polycomb Repressive Complex 2, which adds a chemical mark (H3K27me3) that helps silence gene expression. The gene is considered an oncogene, and its dysregulation has been linked to cancer: chromosomal rearrangements involving EZHIP are seen in low-grade endometrial stromal sarcomas, and activating changes have been found in posterior fossa ependymoma, a brain tumor. The protein is most highly expressed in normal oocytes (egg cells) and may also act as a cancer testis antigen that helps the immune system recognize lung adenocarcinoma cells.
EZHIP is an oncogene whose dysregulation is linked to endometrial stromal sarcoma and posterior fossa ependymoma, but no evidence currently ties this specific p.(Ser460Cys) change to those cancers. The VUS classification reflects the absence of supporting or refuting data; functional studies would be needed to determine whether this substitution alters EZHIP's epigenetic regulatory function.
Final classification VUS: no ACMG/AMP criterion was met, so no pathogenic or benign combination rule was satisfied under the generic ACMG/AMP 2015 framework.
No criteria were applied for this variant.
South Asian 4 / 44,988 |
0.0089% |
Remaining individuals 1 / 26,474 |
0.0038% |
South Asian 3 / 19,079 |
0.016% |
European (non-Finnish) 1 / 81,884 |
0.0012% |
South Asian 2 / 993 |
0.2% |
