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| Growth failure v1.65 | DCAF15 |
Chirag Patel gene: DCAF15 was added gene: DCAF15 was added to Growth failure. Sources: Other Mode of inheritance for gene: DCAF15 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: DCAF15 were set to Cornelia de Lange syndrome Review for gene: DCAF15 was set to AMBER Added comment: ESHG 2023: 3 unrelated cases with CdLS (1 x TOP with MCA, 1 x death @20mths, 1 x living child) Features suggestive of CdLS - DD, microcephaly, CHD, dysmorphism, visual/hearing impairment. WES identified recurrent de novo variant (p.Ser470Phe) in DCAF15 gene. This mediates ubiquitination and degradation of target proteins, and interacts with cohesin complex members (SMC1/SMC3). Protein analysis from individuals showed increased accumulation of ubiquitination-modified proteins and SM3 (GOF mechanism). EpiSign analysis showed same DNA methylation pattern as other CdLS cases/genes. Zebrafish model showed reduced body length, reduced head size, reduced oligodendrocytes, heart defect, aberrant motor neurons, and abnormal response to visual/auditory stimuli. Sources: Other |
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| Growth failure v1.54 | SMC5 |
Zornitza Stark gene: SMC5 was added gene: SMC5 was added to Growth failure. Sources: Literature Mode of inheritance for gene: SMC5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SMC5 were set to 36333305 Phenotypes for gene: SMC5 were set to Multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042, SLF2-related; Atelis syndrome; microcephaly; short stature; ID Review for gene: SMC5 was set to GREEN Added comment: Four individuals from three families with a chromosome breakage disorder and bi-allelic variants in this gene. However, three of the individuals had the same homozygous missense variant. Evidence for functional impact of the variant was limited. However, zebrafish model recapitulated the phenotype and was not rescued by the introduction of this variant, arguing for functional effect. Borderline Amber/Green. Sources: Literature |
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| Growth failure v1.52 | SLF2 |
Zornitza Stark gene: SLF2 was added gene: SLF2 was added to Growth failure. Sources: Literature Mode of inheritance for gene: SLF2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLF2 were set to 36333305 Phenotypes for gene: SLF2 were set to Multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042, SLF2-related; Atelis syndrome; microcephaly; short stature; ID Review for gene: SLF2 was set to GREEN Added comment: Seven individuals from 6 families with a chromosome breakage disorder and bi-allelic variants in this gene (LoF). Functional data including zebrafish model. Sources: Literature |
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| Growth failure v0.11 | BRAF | Zornitza Stark Marked gene: BRAF as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Growth failure v0.11 | BRAF | Zornitza Stark Gene: braf has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Growth failure v0.11 | BRAF | Zornitza Stark Phenotypes for gene: BRAF were changed from Noonan Syndrome; LEOPARD Syndrome; Cardiofaciocutaneous Syndrome; Cardiofaciocutaneous syndrome; Cardio-facio-cutaneous syndrome; LEOPARD syndrome 3 to Noonan syndrome 7, MIM# 613706; Cardiofaciocutaneous syndrome, MIM# 115150 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Growth failure v0.10 | BRAF | Zornitza Stark Publications for gene: BRAF were set to 16474404; 21396583; 16825433; 19206169 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Growth failure v0.9 | BRAF | Zornitza Stark changed review comment from: Well established gene-disease association.; to: Well established gene-disease association. Growth failure, feeding difficulties, short stature are prominent early presenting features. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Growth failure v0.0 | BRAF |
Zornitza Stark gene: BRAF was added gene: BRAF was added to Growth failure in early childhood. Sources: Genomics England PanelApp,Expert Review Green Mode of inheritance for gene: BRAF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: BRAF were set to 16474404; 21396583; 16825433; 19206169 Phenotypes for gene: BRAF were set to Noonan Syndrome; LEOPARD Syndrome; Cardiofaciocutaneous Syndrome; Cardiofaciocutaneous syndrome; Cardio-facio-cutaneous syndrome; LEOPARD syndrome 3 Mode of pathogenicity for gene: BRAF was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments |
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