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| Mosaic skin disorders - deep sequencing v2.2 | ARAF |
Arina Puzriakova Added comment: Comment on list classification: New gene added by Tom Cullup (GOSH). ARAF is not currently associated with any phenotype in OMIM or G2P. Although only two patients have been reported with the same missense variant, functional studies including an animal model provide strong support of pathogenicity (outlined below). Evidence of this variant specific gene-disease relationship is sufficiently compelling but the phenotype is more within scope of the R110 Segmental overgrowth disorders – Deep sequencing panel. Therefore rating as amber on this panel and green on R110. - PMID: 31263281 (2019): To date, only two unrelated patients have been reported with the same missense GoF variant in ARAF (c.640T>C:p.S214P) who both had a complex lymphatic anomaly (no haplotype analysis was done). Cells transduced with ARAF-S214P showed elevated ERK1/2 activity, enhanced lymphangiogenic capacity, and disassembly of actin skeleton and VE-cadherin junctions. A zebrafish model recapitulated the lymphatic phenotype. The cellular, zebrafish and patient clinical phenotypes were all rescued with with a MEK inhibitor. |
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| Mosaic skin disorders - deep sequencing v2.1 | ARAF |
Tom Cullup gene: ARAF was added gene: ARAF was added to Mosaic skin disorders - deep sequencing. Sources: Expert list Mode of inheritance for gene: ARAF was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: ARAF were set to 31263281 Phenotypes for gene: ARAF were set to central conducting lymphatic anomaly Penetrance for gene: ARAF were set to unknown Mode of pathogenicity for gene: ARAF was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: ARAF was set to GREEN Added comment: Two patients described in Li et al with lymphatic anomaly, with same activating missense; functional studies support activating effect including zebrafish model. Sources: Expert list |
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| Mosaic skin disorders - deep sequencing v1.22 | BRAF |
Arina Puzriakova Tag Q4_21_rating was removed from gene: BRAF. Tag Q4_21_NHS_review was removed from gene: BRAF. |
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| Mosaic skin disorders - deep sequencing v1.22 | BRAF | Arina Puzriakova commented on gene: BRAF | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mosaic skin disorders - deep sequencing v1.21 | BRAF |
Arina Puzriakova Source Expert Review Green was added to BRAF. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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| Mosaic skin disorders - deep sequencing v1.18 | BRAF | Eleanor Williams Tag Q4_21_NHS_review tag was added to gene: BRAF. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mosaic skin disorders - deep sequencing v1.12 | BRAF | Eleanor Williams Classified gene: BRAF as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mosaic skin disorders - deep sequencing v1.12 | BRAF | Eleanor Williams Added comment: Comment on list classification: Promoting this gene from grey to amber but with a recommendation for GREEN rating following GMS review. More than 3 cases with tissue specific mosaic missense variants reported and a relevant skin phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mosaic skin disorders - deep sequencing v1.12 | BRAF | Eleanor Williams Gene: braf has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mosaic skin disorders - deep sequencing v1.11 | BRAF | Eleanor Williams Phenotypes for gene: BRAF were changed from Melanocytic naevus syndrome (MIM 137550); Vascular malformations; Noonan syndrome 7 (MIM 613706); LEOPARD syndrome 3 (MIM 613707); Cardio-facio-cutaneous syndrome 1 (MIM 115150) to Melanocytic naevus syndrome, OMIM:137550; Vascular malformations; Noonan syndrome 7 (MIM 613706); LEOPARD syndrome 3 , OMIM:613707; Cardio-facio-cutaneous syndrome 1, OMIM:115150 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mosaic skin disorders - deep sequencing v1.10 | BRAF | Eleanor Williams Publications for gene: BRAF were set to PMID: 31111470; 31891627; 29461977 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mosaic skin disorders - deep sequencing v1.9 | BRAF | Eleanor Williams Tag Q4_21_rating tag was added to gene: BRAF. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mosaic skin disorders - deep sequencing v1.9 | BRAF | Eleanor Williams commented on gene: BRAF | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mosaic skin disorders - deep sequencing v1.5 | BRAF |
Tom Cullup changed review comment from: Note that the primary mosaic phenotypes are melanocytic naevus syndrome (MIM number currently not linked to BRAF) and vascular malformations (no appropriate MIM number currently) - see publications list. Sources: Expert list; to: Note that the primary mosaic phenotypes are melanocytic naevus syndrome (MIM number currently not linked to BRAF) and vascular malformations (no appropriate MIM number currently) - see publications list. Sources: Expert list Fast track form submitted. Note from Prof Kinsler: We have noticed that BRAF is not included on this panel. As a key player in mosaic diseases of various types this was an error somehow in the preparation of the original list. Without it's inclusion on the panel various conditions cannot be properly tested for. For example 7% of Congenital Melanocytic Naevus syndrome are caused by BRAF mosaicism and approximately 5% of Arteriovenous Malformations. |
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| Mosaic skin disorders - deep sequencing v1.5 | BRAF |
Tom Cullup gene: BRAF was added gene: BRAF was added to Mosaic skin disorders - deep sequencing. Sources: Expert list Mode of inheritance for gene: BRAF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: BRAF were set to PMID: 31111470; 31891627; 29461977 Phenotypes for gene: BRAF were set to Melanocytic naevus syndrome (MIM 137550); Vascular malformations; Noonan syndrome 7 (MIM 613706); LEOPARD syndrome 3 (MIM 613707); Cardio-facio-cutaneous syndrome 1 (MIM 115150) Penetrance for gene: BRAF were set to Complete 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 Review for gene: BRAF was set to GREEN Added comment: Note that the primary mosaic phenotypes are melanocytic naevus syndrome (MIM number currently not linked to BRAF) and vascular malformations (no appropriate MIM number currently) - see publications list. Sources: Expert list |
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