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Severe early-onset obesity v4.7 ADCY3 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There is sufficient evidence available for the association of both monoallelic and biallelic variants of this gene to obesity.

The phenotypes of biallelic variants appear severe and early-onset. The age of patients with monoallelic variants ranged from 28 and 57 and its was not clear whether the patients had either monogenic or common form of obesity. Hence, the MOIU should be set as "BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal".; to: Comment on list classification: There is sufficient evidence available for the association of both monoallelic and biallelic variants of this gene to obesity and this gene can be promoted to green rating at the next major update.

The phenotypes of biallelic variants appear severe and early-onset. The age of patients with monoallelic variants ranged from 28 and 57 and its was not clear whether the patients had either monogenic or common form of obesity. Hence, the MOI should be set as "BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal".
Severe early-onset obesity v4.7 ADCY3 Achchuthan Shanmugasundram Classified gene: ADCY3 as Amber List (moderate evidence)
Severe early-onset obesity v4.7 ADCY3 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the association of both monoallelic and biallelic variants of this gene to obesity.

The phenotypes of biallelic variants appear severe and early-onset. The age of patients with monoallelic variants ranged from 28 and 57 and its was not clear whether the patients had either monogenic or common form of obesity. Hence, the MOIU should be set as "BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal".
Severe early-onset obesity v4.7 ADCY3 Achchuthan Shanmugasundram Gene: adcy3 has been classified as Amber List (Moderate Evidence).
Severe early-onset obesity v4.6 ADCY3 Achchuthan Shanmugasundram Phenotypes for gene: ADCY3 were changed from Monogenic severe obesity to Monogenic severe obesity; {Obesity, susceptibility to, BMIQ19}, OMIM:617885
Severe early-onset obesity v4.5 ADCY3 Achchuthan Shanmugasundram changed review comment from: PMID:29311636 - Founder canonical splice variant (c.2433-1G>A) reported in Greenlandic populations demonstrate higher risk of obesity and type 2 diabetes in homozygous individuals.

PMID:29311637 - Four children from three consanguineous Pakistani families were reported with severe early-onset obesity and identified with three different homozygous variants in ADCY3 gene. In addition, an obese boy of European-American descent was identified with heterozygous ADCY3 variants.

PMID:35026759 - Two additional heterozygous variants (c.1658C>T/ p.Ala553Val & c.489C>G/ p.His163Gln) were identified in six Qatari individuals with obesity. However, the authors of this publication struggle to draw a conclusion on the impact of the dominant effect of the variants due to the genetic and biological overlap between monogenic and the common form of obesity.; to: PMID:29311636 - Founder canonical splice variant (c.2433-1G>A) reported in Greenlandic populations demonstrate higher risk of obesity and type 2 diabetes in homozygous individuals.

PMID:29311637 - Four children from three consanguineous Pakistani families were reported with severe early-onset obesity and identified with three different homozygous variants in ADCY3 gene. In addition, an obese boy of European-American descent was identified with heterozygous ADCY3 variants.

PMID:35026759 - Two additional heterozygous variants (c.1658C>T/ p.Ala553Val & c.489C>G/ p.His163Gln) were identified in six Qatari individuals with obesity. However, the authors of this publication struggle to draw a conclusion on the impact of the dominant effect of the variants due to the genetic and biological overlap between monogenic and the common form of obesity.

Autosomal recessive variants in this gene have been associated with phenotype in OMIM (MIM #617885). But, dominant variants have not yet been associated with relevant phenotypes in OMIM.
Severe early-onset obesity v4.5 ADCY3 Achchuthan Shanmugasundram edited their review of gene: ADCY3: Changed publications to: 29311636, 29311637, 35026759
Severe early-onset obesity v4.5 ADCY3 Achchuthan Shanmugasundram Publications for gene: ADCY3 were set to 2931163; 29311637; 35026759
Severe early-onset obesity v4.4 ADCY3 Achchuthan Shanmugasundram Publications for gene: ADCY3 were set to 29311637; 35026759
Severe early-onset obesity v4.3 ADCY3 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: ADCY3.
Severe early-onset obesity v4.3 ADCY3 Achchuthan Shanmugasundram edited their review of gene: ADCY3: Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Severe early-onset obesity v4.3 ADCY3 Achchuthan Shanmugasundram reviewed gene: ADCY3: Rating: GREEN; Mode of pathogenicity: None; Publications: 2931163, 29311637, 35026759; Phenotypes: {Obesity, susceptibility to, BMIQ19}, OMIM:617885; Mode of inheritance: None
Severe early-onset obesity v3.4 ADCY3 Dmitrijs Rots gene: ADCY3 was added
gene: ADCY3 was added to Severe early-onset obesity. Sources: Literature
Mode of inheritance for gene: ADCY3 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: ADCY3 were set to 29311637; 35026759
Phenotypes for gene: ADCY3 were set to Monogenic severe obesity
Penetrance for gene: ADCY3 were set to unknown
Review for gene: ADCY3 was set to GREEN
Added comment: Multiple idependet cases reported with early onset severe obesity and LoF variants ir ADCY3.
Sources: Literature