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| Mendeliome v1.3486 | PPFIA2 |
May Tun Hla Maw changed review comment from: Encodes Liprin-alpha2. Predominantly expressed in brain in the pre- and post-synaptic compartments. Liprin has three domains with N-terminal coiled coil domain (CCD), central (IDRs) and three tandem C-terminal sterile alpha motif (SAM) domains. Gene-disease association: neurodevelopmental disorder. Mode of pathogenicity is unclear; haploinsufficiency has not been proven as disease-causing mechanism. Evidence summary: Previously reported heterozygous de novo variants in two unrelated individuals with a neurodevelopmental disorder. Large cohort studies identified seven additional individuals with rare de novo variants with intellectual disability or developmental delay. Reported variants are mostly missense, and the rest includes non-sense, in-frame deletion, splice site variants. Eight out of these variants are located in the known functional domains (CCD, IDR, SAM). All of these variants were absent in gnomAD. Other phenotypes in these individuals include IUGR, macrocephaly, dystonia, choreatic movement, nystagmus, ataxia, hyperactivity, coarsened gyration, immature opercularization and a coarse corpus callosum, and hypotonia. Functional studies: Homozygous mice with PPFIA2-knockout developed a neurologic phenotype as well as ophthalmologic features. Heterozygous mice did not have apparent phenotype. Sources: Literature; to: Encodes Liprin-alpha2. Predominantly expressed in brain in the pre- and post-synaptic compartments. Liprin has three domains with N-terminal coiled coil domain (CCD), central (IDRs) and three tandem C-terminal sterile alpha motif (SAM) domains. Mode of pathogenicity is unclear; haploinsufficiency has not been proven as disease-causing mechanism. Evidence summary: Previously reported heterozygous de novo variants in two unrelated individuals with a neurodevelopmental disorder. Large cohort studies identified seven additional individuals with rare de novo variants with intellectual disability or developmental delay. Reported variants are mostly missense, and the rest includes non-sense, in-frame deletion, splice site variants. Eight out of these variants are located in the known functional domains (CCD, IDR, SAM). All of these variants were absent in gnomAD. Other phenotypes in these individuals include IUGR, macrocephaly, dystonia, choreatic movement, nystagmus, ataxia, hyperactivity, coarsened gyration, immature opercularization and a coarse corpus callosum, and hypotonia. Functional studies: Homozygous mice with PPFIA2-knockout developed a neurologic phenotype as well as ophthalmologic features. Heterozygous mice did not have apparent phenotype. Sources: Literature |
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| Mendeliome v1.3484 | PPFIA2 | Zornitza Stark Marked gene: PPFIA2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3484 | PPFIA2 | Zornitza Stark Gene: ppfia2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3484 | PPFIA2 | Zornitza Stark Mode of pathogenicity for gene: PPFIA2 was changed from Other to None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3483 | PPFIA2 | Zornitza Stark Classified gene: PPFIA2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3483 | PPFIA2 | Zornitza Stark Gene: ppfia2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3479 | PPFIA2 |
May Tun Hla Maw gene: PPFIA2 was added gene: PPFIA2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PPFIA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PPFIA2 were set to 41044885 Phenotypes for gene: PPFIA2 were set to Neurodevelopmental disorder, MONDO:0700092, PPFIA2 related Mode of pathogenicity for gene: PPFIA2 was set to Other Review for gene: PPFIA2 was set to GREEN Added comment: Encodes Liprin-alpha2. Predominantly expressed in brain in the pre- and post-synaptic compartments. Liprin has three domains with N-terminal coiled coil domain (CCD), central (IDRs) and three tandem C-terminal sterile alpha motif (SAM) domains. Gene-disease association: neurodevelopmental disorder. Mode of pathogenicity is unclear; haploinsufficiency has not been proven as disease-causing mechanism. Evidence summary: Previously reported heterozygous de novo variants in two unrelated individuals with a neurodevelopmental disorder. Large cohort studies identified seven additional individuals with rare de novo variants with intellectual disability or developmental delay. Reported variants are mostly missense, and the rest includes non-sense, in-frame deletion, splice site variants. Eight out of these variants are located in the known functional domains (CCD, IDR, SAM). All of these variants were absent in gnomAD. Other phenotypes in these individuals include IUGR, macrocephaly, dystonia, choreatic movement, nystagmus, ataxia, hyperactivity, coarsened gyration, immature opercularization and a coarse corpus callosum, and hypotonia. Functional studies: Homozygous mice with PPFIA2-knockout developed a neurologic phenotype as well as ophthalmologic features. Heterozygous mice did not have apparent phenotype. Sources: Literature |
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