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Skeletal ciliopathies v5.4 FAM149B1 Achchuthan Shanmugasundram Tag Q3_24_promote_green was removed from gene: FAM149B1.
Skeletal ciliopathies v5.4 FAM149B1 Achchuthan Shanmugasundram commented on gene: FAM149B1: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Skeletal ciliopathies v5.3 FAM149B1 Achchuthan Shanmugasundram Source NHS GMS was added to FAM149B1.
Source Expert Review Green was added to FAM149B1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal ciliopathies v4.6 FAM149B1 Achchuthan Shanmugasundram Classified gene: FAM149B1 as Amber List (moderate evidence)
Skeletal ciliopathies v4.6 FAM149B1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (five unrelated families and two different variants) for promoting this gene to green rating in the next GMS update.
Skeletal ciliopathies v4.6 FAM149B1 Achchuthan Shanmugasundram Gene: fam149b1 has been classified as Amber List (Moderate Evidence).
Skeletal ciliopathies v4.6 FAM149B1 Achchuthan Shanmugasundram Phenotypes for gene: FAM149B1 were changed from Joubert syndrome 36, OMIM:618763 to Joubert syndrome 36, OMIM:618763
Skeletal ciliopathies v4.5 FAM149B1 Achchuthan Shanmugasundram Phenotypes for gene: FAM149B1 were changed from Joubert syndrome; oral-facial-digital syndrome; OFD VI to Joubert syndrome 36, OMIM:618763
Skeletal ciliopathies v4.5 FAM149B1 Achchuthan Shanmugasundram Publications for gene: FAM149B1 were set to 30905400; 34828254
Skeletal ciliopathies v4.4 FAM149B1 Achchuthan Shanmugasundram Publications for gene: FAM149B1 were set to 30905400
Skeletal ciliopathies v4.3 FAM149B1 Achchuthan Shanmugasundram Tag Q3_24_promote_green tag was added to gene: FAM149B1.
Skeletal ciliopathies v4.3 FAM149B1 Achchuthan Shanmugasundram edited their review of gene: FAM149B1: Added comment: PMID:34828254 reported the identification of homozygous FAM149B1 variant (c.354_357delinsCACTC/ p.Gln118Hisfs*20) in three adult siblings from a large consanguineous family from Saudi Arabia. This variant is similar to one of the two variants that were previously reported in three unrelated families from Saudi Arabia (c.356_357del/ p.Lys119Ilefs∗18).

This gene has been associated with relevant phenotypes in OMIM (MIM #618763) and Gene2Phenotype (with 'strong' rating on the DD panel).; Changed rating: GREEN; Changed publications to: 34828254; Changed phenotypes to: Joubert syndrome 36, OMIM:618763; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal ciliopathies v3.11 FAM149B1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: FAM149B1.
Skeletal ciliopathies v3.11 FAM149B1 Achchuthan Shanmugasundram commented on gene: FAM149B1
Skeletal ciliopathies v0.15 FAM149B1 Eleanor Williams changed review comment from: Comment on list classification: 3 founder variant cases reported plus one other. Some functional data. Changing rating from red to amber based on the 2 independent cases reported.; to: Comment on list classification: 3 founder variant cases reported plus one other. Some functional data. Changing rating from red to amber based on the 2 independent cases reported. However, the skeletal phenotypes are polydactyly/clinodactyly only.
Skeletal ciliopathies v0.15 FAM149B1 Eleanor Williams Classified gene: FAM149B1 as Amber List (moderate evidence)
Skeletal ciliopathies v0.15 FAM149B1 Eleanor Williams Added comment: Comment on list classification: 3 founder variant cases reported plus one other. Some functional data. Changing rating from red to amber based on the 2 independent cases reported.
Skeletal ciliopathies v0.15 FAM149B1 Eleanor Williams Gene: fam149b1 has been classified as Amber List (Moderate Evidence).
Skeletal ciliopathies v0.14 FAM149B1 Eleanor Williams gene: FAM149B1 was added
gene: FAM149B1 was added to Skeletal ciliopathies. Sources: Literature
Mode of inheritance for gene: FAM149B1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAM149B1 were set to 30905400
Phenotypes for gene: FAM149B1 were set to Joubert syndrome; oral-facial-digital syndrome; OFD VI
Review for gene: FAM149B1 was set to AMBER
Added comment: PMID: 30905400 - Shaheen et al 2019 - report 4 cases in which homozygous variants in the FAM149B1 gene are found in patients with a ciliopathy phenotype that most closely matches Joubert syndrome or Joubert syndrome/oral-facial-digital syndrome (OFD VI) . 3 of the cases in Consanguinity families of Arab origin have the same c.356_357del (p.Lys119Ilefs∗18) variant and haplotype analysis suggests a founder mutation. The fourth case in a Turkish family with Joubert syndrome was found to have a different homozygous truncating variant in the same gene (c.439C>T [p.Gln147∗])). Both variants are predicted to result in truncated proteins.
Functional studies - FAM149B1 encodes a protein of unknown function and mutant fibroblasts were found to have normal ciliogenesis potential. But some cilia-related abnormalities were observed in these cells: abnormal accumulation IFT complex at the distal tips of the cilia, which assumed bulbous appearance, increased length of the primary cilium, and dysregulated SHH signaling.
Sources: Literature