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| Haematological malignancies cancer susceptibility v3.3 | MBD4 |
Arina Puzriakova Tag Q3_22_rating was removed from gene: MBD4. Tag Q3_22_expert_review was removed from gene: MBD4. |
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| Haematological malignancies cancer susceptibility v3.3 | MBD4 | Arina Puzriakova edited their review of gene: MBD4: Added comment: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Haematological malignancies cancer susceptibility v3.2 | MBD4 |
Arina Puzriakova Source Expert Review Green was added to MBD4. Source NHS GMS was added to MBD4. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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| Haematological malignancies cancer susceptibility v2.38 | MBD4 |
Arina Puzriakova changed review comment from: Re-tagging on this panel following a separate Green expert review on a different GMS panel (R347, R211) to ensure that if the decision is made to include the gene, all panels are appropriately updated.; to: Re-tagging on this panel following a new Green expert review by Dr Claire Palles on a different GMS panel (R347, R211) to ensure that if the decision is made to include the gene, all panels are appropriately updated. 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. |
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| Haematological malignancies cancer susceptibility v2.36 | MBD4 | Eleanor Williams Tag Q3_22_rating tag was added to gene: MBD4. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Haematological malignancies cancer susceptibility v2.34 | MBD4 | Arina Puzriakova Phenotypes for gene: MBD4 were changed from AML, colonic polyps, uveal melanoma, glioblastoma to Multi-organ tumour predisposition syndrome; Adenomatous colorectal polyposis; Colorectal cancer; Acute myeloid leukemia; Uveal melanoma | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Haematological malignancies cancer susceptibility v2.33 | MBD4 | Arina Puzriakova Tag Q3_22_expert_review tag was added to gene: MBD4. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Haematological malignancies cancer susceptibility v2.33 | MBD4 | Arina Puzriakova commented on gene: MBD4: Re-tagging on this panel following a separate Green expert review on a different GMS panel (R347, R211) to ensure that if the decision is made to include the gene, all panels are appropriately updated. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Haematological malignancies cancer susceptibility v2.33 | MBD4 | Arina Puzriakova changed review comment from: Palles et al. 2022 (PMID: 35460607) reported on 5 individuals from 4 families with biallelic MBD4 variants who had a personal and/or family history of adenomatous colorectal polyposis (5/5), AML (1/5 personal, 2/5 family), and uveal melanoma (2/5 personal). Consistent with previous studies, MBD4-deficient colorectal adenomas showed a significantly increased mutational burden compared to sporadic colorectal tumours, which were mostly attributable to an excess of CpG>TpG transitions.; to: Palles et al. 2022 (PMID: 35460607) reported on 5 individuals from 4 families with biallelic MBD4 variants who had a personal and/or family history of adenomatous colorectal polyposis (5/5), AML (1/5 personal, 2 family), and uveal melanoma (2/5 personal). Consistent with previous studies, MBD4-deficient colorectal adenomas showed a significantly increased mutational burden compared to sporadic colorectal tumours, which were mostly attributable to an excess of CpG>TpG transitions. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Haematological malignancies cancer susceptibility v2.33 | MBD4 | Arina Puzriakova changed review comment from: Palles et al. 2022 (PMID: 35460607) reported on 5 individuals from 4 families with biallelic MBD4 variants who had a personal and/or family history of adenomatous colorectal polyposis (5/5), AML (1/5 personal), and uveal melanoma (2/5 personal). Consistent with previous studies, MBD4-deficient colorectal adenomas showed a significantly increased mutational burden compared to sporadic colorectal tumours, which were mostly attributable to an excess of CpG>TpG transitions.; to: Palles et al. 2022 (PMID: 35460607) reported on 5 individuals from 4 families with biallelic MBD4 variants who had a personal and/or family history of adenomatous colorectal polyposis (5/5), AML (1/5 personal, 2/5 family), and uveal melanoma (2/5 personal). Consistent with previous studies, MBD4-deficient colorectal adenomas showed a significantly increased mutational burden compared to sporadic colorectal tumours, which were mostly attributable to an excess of CpG>TpG transitions. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Haematological malignancies cancer susceptibility v2.33 | MBD4 | Arina Puzriakova edited their review of gene: MBD4: Added comment: Palles et al. 2022 (PMID: 35460607) reported on 5 individuals from 4 families with biallelic MBD4 variants who had a personal and/or family history of adenomatous colorectal polyposis (5/5), AML (1/5 personal), and uveal melanoma (2/5 personal). Consistent with previous studies, MBD4-deficient colorectal adenomas showed a significantly increased mutational burden compared to sporadic colorectal tumours, which were mostly attributable to an excess of CpG>TpG transitions.; Changed publications to: 12417741, 30049810, 32239153, 35460607; Changed phenotypes to: Multi-organ tumour predisposition syndrome, Adenomatous colorectal polyposis, Colorectal cancer, Acute myeloid leukemia, Uveal melanoma | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Haematological malignancies cancer susceptibility v2.23 | MBD4 | Arina Puzriakova Tag for-review was removed from gene: MBD4. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Haematological malignancies cancer susceptibility v2.23 | MBD4 | Arina Puzriakova commented on gene: MBD4: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Haematological malignancies cancer susceptibility v2.12 | MBD4 | Arina Puzriakova Classified gene: MBD4 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Haematological malignancies cancer susceptibility v2.12 | MBD4 |
Arina Puzriakova Added comment: Comment on list classification: New gene added by Kiran Tawana (Addenbrooke's Hospital, Cambridge) with a Green expert review rating. Studies indicate that while germline MBD4 deficiency alone does not drive malignant transformation, it may alter the mutational spectrum and in turn modify susceptibility and predisposition to cancers such as AML. Therefore, rating this gene as Amber with the recommendation of review by the GMS team with regards to whether such alterations are within the scope of this panel (added 'for-review' tag) |
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| Haematological malignancies cancer susceptibility v2.12 | MBD4 | Arina Puzriakova Gene: mbd4 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Haematological malignancies cancer susceptibility v2.11 | MBD4 | Arina Puzriakova Tag for-review tag was added to gene: MBD4. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Haematological malignancies cancer susceptibility v2.11 | MBD4 | Arina Puzriakova reviewed gene: MBD4: Rating: ; Mode of pathogenicity: None; Publications: 30049810; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Haematological malignancies cancer susceptibility v2.5 | MBD4 |
Kiran Tawana gene: MBD4 was added gene: MBD4 was added to Haematological malignancies cancer susceptibility. Sources: Literature Mode of inheritance for gene: MBD4 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MBD4 were set to PMID: 30049810; PMID: 29760383; PMID: 32239153 Phenotypes for gene: MBD4 were set to AML, colonic polyps, uveal melanoma, glioblastoma Penetrance for gene: MBD4 were set to Complete Review for gene: MBD4 was set to GREEN Added comment: Sources: Literature |
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