| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Mendeliome v1.1787 | AGTR2 | Zornitza Stark Marked gene: AGTR2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1787 | AGTR2 | Zornitza Stark Gene: agtr2 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1787 | AGTR2 |
Zornitza Stark changed review comment from: Variants in AGTR2 have been reported in individuals presenting various neurodevelopmental phenotypes, including intellectual disability, autistic features, epileptic seizures, speech delay, restlessness, and hyperactivity, as early as 2002. Per criteria outlined by the ClinGen Lumping and Splitting Working Group, we found no difference in molecular mechanism, inheritance pattern, or phenotypic variability. Therefore, for the purposes of this curation, all of these features have been lumped into one disease entity, X-linked complex neurodevelopmental disorder. Although eight unique variants, including missense and truncating, have been reported in affected humans, the majority (six) have been ruled out from disease-causality based on high frequency in control populations (Piton et al., PMID 23871722), occurrence in unaffected males (Erdmann et al., PMID 14722754), non-segregation within a family (Bienvenu et al., PMID 12746399), and lack of enrichment in patients in a case-control study (Huang et al., PMID 16283672). Given that the two remaining variants are missense with no supporting functional evidence, and AGTR2 was the only gene sequenced in each case, the ClinGen Intellectual Disability and Autism Working Group recommended awarding 0 points for these variants. There are two AGTR2 mouse models which collectively show altered neuronal spine morphology, spatial memory impairment, delayed learning, and reduced exploratory behavior (PMIDs 18335189 and 7477267). Sources: Expert Review; to: DISPUTED by ClinGen: Variants in AGTR2 have been reported in individuals presenting various neurodevelopmental phenotypes, including intellectual disability, autistic features, epileptic seizures, speech delay, restlessness, and hyperactivity, as early as 2002. Per criteria outlined by the ClinGen Lumping and Splitting Working Group, we found no difference in molecular mechanism, inheritance pattern, or phenotypic variability. Therefore, for the purposes of this curation, all of these features have been lumped into one disease entity, X-linked complex neurodevelopmental disorder. Although eight unique variants, including missense and truncating, have been reported in affected humans, the majority (six) have been ruled out from disease-causality based on high frequency in control populations (Piton et al., PMID 23871722), occurrence in unaffected males (Erdmann et al., PMID 14722754), non-segregation within a family (Bienvenu et al., PMID 12746399), and lack of enrichment in patients in a case-control study (Huang et al., PMID 16283672). Given that the two remaining variants are missense with no supporting functional evidence, and AGTR2 was the only gene sequenced in each case, the ClinGen Intellectual Disability and Autism Working Group recommended awarding 0 points for these variants. There are two AGTR2 mouse models which collectively show altered neuronal spine morphology, spatial memory impairment, delayed learning, and reduced exploratory behavior (PMIDs 18335189 and 7477267). Sources: Expert Review |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1787 | AGTR2 |
Zornitza Stark gene: AGTR2 was added gene: AGTR2 was added to Mendeliome. Sources: Expert Review disputed tags were added to gene: AGTR2. Mode of inheritance for gene: AGTR2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: AGTR2 were set to X-linked complex neurodevelopmental disorder MONDO:0100148 Review for gene: AGTR2 was set to RED Added comment: Variants in AGTR2 have been reported in individuals presenting various neurodevelopmental phenotypes, including intellectual disability, autistic features, epileptic seizures, speech delay, restlessness, and hyperactivity, as early as 2002. Per criteria outlined by the ClinGen Lumping and Splitting Working Group, we found no difference in molecular mechanism, inheritance pattern, or phenotypic variability. Therefore, for the purposes of this curation, all of these features have been lumped into one disease entity, X-linked complex neurodevelopmental disorder. Although eight unique variants, including missense and truncating, have been reported in affected humans, the majority (six) have been ruled out from disease-causality based on high frequency in control populations (Piton et al., PMID 23871722), occurrence in unaffected males (Erdmann et al., PMID 14722754), non-segregation within a family (Bienvenu et al., PMID 12746399), and lack of enrichment in patients in a case-control study (Huang et al., PMID 16283672). Given that the two remaining variants are missense with no supporting functional evidence, and AGTR2 was the only gene sequenced in each case, the ClinGen Intellectual Disability and Autism Working Group recommended awarding 0 points for these variants. There are two AGTR2 mouse models which collectively show altered neuronal spine morphology, spatial memory impairment, delayed learning, and reduced exploratory behavior (PMIDs 18335189 and 7477267). Sources: Expert Review |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||