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| Fetal anomalies v0.372 | CNOT1 | Rebecca Foulger Phenotypes for gene: CNOT1 were changed from pancreatic agenesis and holoprosencephaly syndrome to Holoprosencephaly 12, with or without pancreatic agenesis, 618500 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.311 | CNOT1 | Rebecca Foulger edited their review of gene: CNOT1: Added comment: Upgraded from Amber to Green following advice from Anna de Burca (Genomics England clinical team) and a Fetal Working Group call on July 19th 2019. Phenotypes are relevant to this panel (holoprosencephaly and pancreatic agenesis), sufficient cases (4/5), although phenotype may be variant-specific.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.310 | CNOT1 |
Rebecca Foulger Source Expert Review Green was added to CNOT1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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| Fetal anomalies v0.284 | CNOT1 | Rebecca Foulger commented on gene: CNOT1: Keep as amber and added watchlist tag on advice from Helen Brittain (Genomics England Clinical Fellow);this might be a specific variant-related phenotype, and there is insufficient evidence for the gene in general at present. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.248 | CNOT1 | Rebecca Foulger Classified gene: CNOT1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.248 | CNOT1 | Rebecca Foulger Added comment: Comment on list classification: Kept rating as Amber awaiting clinical review. In summary: Sufficient (five) unrelated cases from two 2019 papers (PMID:31006513 and PMID:31006510) with holoprosencephaly, and pancreatic agenesis in 4/5 cases. The same heterozygous variant was recorded in all five individuals and authors of PMID:31006513 suggest phenotype is variant-specific rather than LOF. Mice require a homozygous variant to display a phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.248 | CNOT1 | Rebecca Foulger Gene: cnot1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.247 | CNOT1 | Rebecca Foulger commented on gene: CNOT1: Kruszka et al., 2019 (PMID:31006510) report two unrelated individuals with semilobar holoprosencephaly who have the identical de novo missense variant in the gene CNOT1. (c.1603C>T [p.Arg535Cys]). Proband 1 was born after a pregnancy complicated by IUGR. Additional medical problems include diabetes, pancreatice exocrine insufficiency and facial characteristics. No diabetic or pancreatic phenotype was recorded for proband 2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.247 | CNOT1 | Rebecca Foulger commented on gene: CNOT1: De Franco et al., 2019 (PMID:31006513) investigated a cohort of 107 individuals with pancreatic agenesis and definite/possible holoprosencephaly, and identified a heterozygous missense variant in CNOT1 (NM_016284.4; c.1603C>T (p.Arg535Cys)) in three unrelated individuals. The variant was de novo in two individuals, and was not present in the DNA sample from the third individual's father (maternal sample was unavailable). Mice required a homozygous variant to display a phenotype: in homozygous mice embryos (embryonically lethal) morphological abnormalities were apparent upon dissection including edema, a smaller dorsal pancreas, and exencephaly. The DDD study identified de novo CNOT1 variants in three individuals with developmental delay but none had holoprosencephaly, diabetes or pancreatic or neurological structural malformations. The authors therefore suggest that a mutation-specific mechanism rather than LOF is responsible for the pancreatic and holoprosencephaly phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.247 | CNOT1 | Rebecca Foulger reviewed gene: CNOT1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.246 | CNOT1 |
Rebecca Foulger gene: CNOT1 was added gene: CNOT1 was added to Fetal anomalies. Sources: DD-Gene2Phenotype,Expert Review Amber Mode of inheritance for gene: CNOT1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: CNOT1 were set to 31006510; 31006513 Phenotypes for gene: CNOT1 were set to pancreatic agenesis and holoprosencephaly syndrome Mode of pathogenicity for gene: CNOT1 was set to Other - please provide details in the comments |
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