| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Inherited polyposis and early onset colorectal cancer - germline testing v2.4 | MBD4 |
Arina Puzriakova Tag Q3_22_rating was removed from gene: MBD4. Tag Q3_22_NHS_review was removed from gene: MBD4. Tag Q3_22_expert_review was removed from gene: MBD4. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inherited polyposis and early onset colorectal cancer - germline testing v2.4 | MBD4 | Arina Puzriakova Source NHS GMS was added to MBD4. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inherited polyposis and early onset colorectal cancer - germline testing v2.3 | MBD4 | Arina Puzriakova commented on gene: MBD4: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inherited polyposis and early onset colorectal cancer - germline testing v1.32 | MBD4 |
Arina Puzriakova changed review comment from: Comment on list classification: This gene will be flagged for GMS expert review to determine the suitability of MBD4 for malignancy predisposition testing. MBD4 was first added by an external reviewer to the 'Haematological malignancies cancer susceptibility' panel (https://panelapp.genomicsengland.co.uk/panels/59/gene/MBD4/), however after GMS consideration it was decided that it should remain amber (v2.23). Loss of MBD4 leads to an accumulation of somatic CpG>TpG transitions, consistent with MBD4 function which involves repair of G:T mismatches resulting from deamination of 5'-methylcytosine. Germline MBD4 inactivation can therefore lead to somatic variation (i.e. CpG>TpG) in well-down cancer driver genes, in turn conferring cancer susceptibility. Although MBD4 itself does not directly drive oncogenesis, evidence suggests it may modify disease risk as shown by multiple cases reported in literature with this distinctive mutational signature. Given that there are now two separate Green clinical reviews suggesting this gene, it will again be flagged for further GMS review.; to: Comment on list classification: This gene will be flagged for GMS expert review to determine the suitability of MBD4 for malignancy predisposition testing. MBD4 was first added by an external reviewer to the 'Haematological malignancies cancer susceptibility' panel (https://panelapp.genomicsengland.co.uk/panels/59/gene/MBD4/), however after GMS consideration it was decided that it should remain amber (v2.23). Loss of MBD4 leads to an accumulation of somatic CpG>TpG transitions, consistent with MBD4 function which involves repair of G:T mismatches resulting from deamination of 5'-methylcytosine. Germline MBD4 inactivation can therefore lead to somatic variation (i.e. CpG>TpG) in well-known cancer driver genes, in turn conferring cancer susceptibility. Although MBD4 itself does not directly drive oncogenesis, evidence suggests it may modify disease risk as shown by multiple cases reported in literature with this distinctive mutational signature. Given that there are now two separate Green clinical reviews suggesting this gene, it will again be flagged for further GMS review. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inherited polyposis and early onset colorectal cancer - germline testing v1.32 | MBD4 | Arina Puzriakova Classified gene: MBD4 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inherited polyposis and early onset colorectal cancer - germline testing v1.32 | MBD4 |
Arina Puzriakova Added comment: Comment on list classification: This gene will be flagged for GMS expert review to determine the suitability of MBD4 for malignancy predisposition testing. MBD4 was first added by an external reviewer to the 'Haematological malignancies cancer susceptibility' panel (https://panelapp.genomicsengland.co.uk/panels/59/gene/MBD4/), however after GMS consideration it was decided that it should remain amber (v2.23). Loss of MBD4 leads to an accumulation of somatic CpG>TpG transitions, consistent with MBD4 function which involves repair of G:T mismatches resulting from deamination of 5'-methylcytosine. Germline MBD4 inactivation can therefore lead to somatic variation (i.e. CpG>TpG) in well-down cancer driver genes, in turn conferring cancer susceptibility. Although MBD4 itself does not directly drive oncogenesis, evidence suggests it may modify disease risk as shown by multiple cases reported in literature with this distinctive mutational signature. Given that there are now two separate Green clinical reviews suggesting this gene, it will again be flagged for further GMS review. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inherited polyposis and early onset colorectal cancer - germline testing v1.32 | MBD4 | Arina Puzriakova Gene: mbd4 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inherited polyposis and early onset colorectal cancer - germline testing v1.31 | MBD4 |
Arina Puzriakova Tag Q3_22_rating tag was added to gene: MBD4. Tag Q3_22_NHS_review tag was added to gene: MBD4. Tag Q3_22_expert_review tag was added to gene: MBD4. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inherited polyposis and early onset colorectal cancer - germline testing v1.31 | MBD4 | Arina Puzriakova Entity copied from GI tract tumours v1.22 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inherited polyposis and early onset colorectal cancer - germline testing v1.31 | MBD4 |
Arina Puzriakova gene: MBD4 was added gene: MBD4 was added to Inherited polyposis. Sources: Literature,Expert Review Amber Mode of inheritance for gene: MBD4 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MBD4 were set to 12417741; 30049810; 32239153; 35460607 Phenotypes for gene: MBD4 were set to Multi-organ tumour predisposition syndrome; Adenomatous colorectal polyposis; Colorectal cancer; Acute myeloid leukemia; Uveal melanoma Penetrance for gene: MBD4 were set to Complete |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||