{"count":220324,"next":"https://panelapp-aus.org/api/v1/activities/?format=json&page=1319","previous":"https://panelapp-aus.org/api/v1/activities/?format=json&page=1317","results":[{"created":"2021-05-26T17:38:53.822902+10:00","panel_name":"Additional findings_Adult","panel_id":221,"panel_version":"0.124","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: PALB2 as Green List (high evidence)","entity_name":"PALB2","entity_type":"gene"},{"created":"2021-05-26T17:38:53.813081+10:00","panel_name":"Additional findings_Adult","panel_id":221,"panel_version":"0.124","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: palb2 has been classified as Green List (High Evidence).","entity_name":"PALB2","entity_type":"gene"},{"created":"2021-05-26T17:38:44.841843+10:00","panel_name":"Additional findings_Adult","panel_id":221,"panel_version":"0.123","user_name":"Zornitza Stark","item_type":"entity","text":"gene: PALB2 was added\ngene: PALB2 was added to Additional findings_Adult. Sources: Expert list\nMode of inheritance for gene: PALB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: PALB2 were set to 34012068\nPhenotypes for gene: PALB2 were set to {Breast cancer, susceptibility to}\t114480\nReview for gene: PALB2 was set to GREEN\nAdded comment: Included in ACMG V3.0 as risk of breast cancer meets penetrance threshold. \nSources: Expert list","entity_name":"PALB2","entity_type":"gene"},{"created":"2021-05-26T17:37:14.666632+10:00","panel_name":"Additional findings_Adult","panel_id":221,"panel_version":"0.122","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: MAX as ready","entity_name":"MAX","entity_type":"gene"},{"created":"2021-05-26T17:37:14.656665+10:00","panel_name":"Additional findings_Adult","panel_id":221,"panel_version":"0.122","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: max has been classified as Green List (High Evidence).","entity_name":"MAX","entity_type":"gene"},{"created":"2021-05-26T17:37:10.955013+10:00","panel_name":"Additional findings_Adult","panel_id":221,"panel_version":"0.122","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: MAX as Green List (high evidence)","entity_name":"MAX","entity_type":"gene"},{"created":"2021-05-26T17:37:10.944642+10:00","panel_name":"Additional findings_Adult","panel_id":221,"panel_version":"0.122","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: max has been classified as Green List (High Evidence).","entity_name":"MAX","entity_type":"gene"},{"created":"2021-05-26T17:37:02.072985+10:00","panel_name":"Additional findings_Adult","panel_id":221,"panel_version":"0.121","user_name":"Zornitza Stark","item_type":"entity","text":"gene: MAX was added\ngene: MAX was added to Additional findings_Adult. Sources: Expert list\nMode of inheritance for gene: MAX was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: MAX were set to 34012068\nPhenotypes for gene: MAX were set to {Pheochromocytoma, susceptibility to}\t171300\nReview for gene: MAX was set to GREEN\nAdded comment: Recommended on ACMG V3.0 list as penetrance met threshold to include with other PGL/PCC genes. \nSources: Expert list","entity_name":"MAX","entity_type":"gene"},{"created":"2021-05-26T10:40:02.518097+10:00","panel_name":"Cone-rod Dystrophy","panel_id":3147,"panel_version":"0.23","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: SLC6A6 were changed from Cone-rod retinopathy; cardiomyopathy to Hypotaurinaemic retinal degeneration and cardiomyopathy (HTRDC), MIM#145350; Cone-rod retinopathy; cardiomyopathy","entity_name":"SLC6A6","entity_type":"gene"},{"created":"2021-05-26T10:39:49.496882+10:00","panel_name":"Cone-rod Dystrophy","panel_id":3147,"panel_version":"0.22","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: SLC6A6: Changed phenotypes: Hypotaurinaemic retinal degeneration and cardiomyopathy (HTRDC), MIM#145350, Early retinal degeneration, cardiomyopathy","entity_name":"SLC6A6","entity_type":"gene"},{"created":"2021-05-26T10:38:58.813202+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.7676","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: SLC6A6 were changed from Early retinal degeneration; cardiomyopathy to Hypotaurinaemic retinal degeneration and cardiomyopathy (HTRDC), MIM#145350; Early retinal degeneration; cardiomyopathy","entity_name":"SLC6A6","entity_type":"gene"},{"created":"2021-05-26T10:38:04.742322+10:00","panel_name":"Dilated Cardiomyopathy","panel_id":95,"panel_version":"1.2","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: SLC6A6 were changed from Early retinal degeneration; cardiomyopathy to Hypotaurinaemic retinal degeneration and cardiomyopathy (HTRDC), MIM#145350; Early retinal degeneration; cardiomyopathy","entity_name":"SLC6A6","entity_type":"gene"},{"created":"2021-05-26T10:37:28.677797+10:00","panel_name":"Dilated Cardiomyopathy","panel_id":95,"panel_version":"1.1","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: SLC6A6: Changed phenotypes: Hypotaurinaemic retinal degeneration and cardiomyopathy (HTRDC), MIM#145350, Early retinal degeneration, cardiomyopathy","entity_name":"SLC6A6","entity_type":"gene"},{"created":"2021-05-26T04:31:30.234065+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3786","user_name":"Konstantinos Varvagiannis","item_type":"entity","text":"changed review comment from: Ni et al (2021 - PMID: 33473208) describe the phenotype of 8 children (belonging to 4 families - 2 of which consanguineous) homozygous for a UFSP2 missense variant [NM_018359.5:c.344T>A; p.(Val115Glu)].\r\n\r\nMembers of a broader consanguineous pedigree from Pakistan with 3 affected children with epilepsy and DD and ID underwent exome sequencing. All affected individuals were homozygous for the specific SNV with their parents (2 parent pairs, in both cases first cousins) being heterozygous. An unaffected sib was homozygous for the wt allele. Through genematching platforms 3 additional families with similarly affected individuals and homozygosity for the same variant were recruited. These additional families were from Pakistan (1/3) and Afganistan (2/3). \r\n\r\nBased on ROH analysis from the broader first pedigree and an additional family the authors concluded on a single shared region of homozygosity on chr 4q. Lack of ES data did not allow verification of whether 2/4 families shared the same haplotype with the other 2. \r\n\r\nThe authors calculated the probability of the genotype-phenotype cosegragation occurring by chance (0.009) and this was lower than the recommended criterion (0.06) for strong evidence of pathogenicity.\r\n\r\nShared features included abnormal tone in most (hypotonia 6/8, limb hypertonia 1/8), seizures (8/8 - onset 2d - 7m), severe DD with speech delay/absent speech (8/8), ID (8/8), strabismus (6/8).\r\n\r\nUFSP2 encodes UFM1-specific protease 2 involved in UFmylation, a post-translational protein modification. As summarized by the authors the cysteine protease encoded by this gene (as is also the case for UFSP1) cleaves UFM1 in the initial step of UFMylation. Apart from producing mature UFM1, the 2 proteases have also the ability to release UFM1 from UFMylated proteins, in the process of de-UFMylation. [several refs. provided]\r\n\r\nUFMylation is important in brain development with mutations in genes encoding other components of the pathway reported in other NDD disorders (incl. UFM1, UBA5, UFC1).\r\n\r\nAdditional studies were carried to provide evidence for pathogenicity of this variant.\r\n\r\nSkin biopsies from 3 individuals were carried out to establish fibroblast cultures. Immunoblotting revealed reduced UFSP2 levels relative to controls. mRNA levels measured by qRT-PCR revealed no differences compared to controls altogether suggesting normal mRNA but reduced protein stability. \r\n\r\nThe authors demonstrated increased levels of UFM1-conjugated proteins (incl. DDRGK1, or TRIP4). Ectopic expression of wt UFSP2 normalized the levels of UFMylated proteins in the fibroblasts which was not the case for the V115E variant. Further the variant was difficult to detect by immunoblotting consistent with an effect on protein destabilization.\r\n\r\nAlthough disruption of UFMylation induces ER stress, this was not shown to occur in patient fibroblast lines, when assessed for ER stress markers.\r\n\r\nEvaluation of data from the GTEx project, concerning UFSP2 as well as well as DDRGK1 or TRIP4 - an UFMylation target - revealed relevant expression in multiple regions of the human brain.\r\n\r\nOverall the authors provide evidence for defective de-UFMylation in patient fibroblasts (presence of increased UFMylation marks). The authors stress out that the effect of the variant in UFMylation in brain is unknown, as UFSP1 or other enzymes might compensate in the presence of hypomorphic UFSP2 mutants.\r\n\r\nBiallelic UFSP2 variants have previously been reported in 2 skeletal dysplasias [# 142669. BEUKES HIP DYSPLASIA; BHD and # 617974. SPONDYLOEPIMETAPHYSEAL DYSPLASIA, DI ROCCO TYPE; SEMDDR]. These disorders are not characterized by neurological dysfunction or epilepsy. The authors underscore the fact that variants identified in these disorders (Y290H, D526A, H428R) localize within the C-terminal catalytic (peptidase) domain [aa 278 – 461] while the variant here identified lies in the N-terminal substrate binding domain affecting protein stability/abundance.\r\n\r\nIn OMIM, only the 2 aforementioned disorders are currently associated with biallelic UFSP2 mutations. There is no associated phenotype in G2P. SysID includes UFSP2 among the primary ID genes.\r\n\r\nYou may consider inclusion in the current panel with amber/green rating. \nSources: Literature; to: Ni et al (2021 - PMID: 33473208) describe the phenotype of 8 children (belonging to 4 families - 2 of which consanguineous) homozygous for a UFSP2 missense variant [NM_018359.5:c.344T>A; p.(Val115Glu)].\r\n\r\nMembers of a broader consanguineous pedigree from Pakistan with 3 affected children with epilepsy and DD and ID underwent exome sequencing. All affected individuals were homozygous for the specific SNV with their parents (2 parent pairs, in both cases first cousins) being heterozygous. An unaffected sib was homozygous for the wt allele. Through genematching platforms 3 additional families with similarly affected individuals and homozygosity for the same variant were recruited. These additional families were from Pakistan (1/3) and Afganistan (2/3). \r\n\r\nBased on ROH analysis from the broader first pedigree and an additional family the authors concluded on a single shared region of homozygosity on chr 4q. Lack of ES data did not allow verification of whether 2/4 families shared the same haplotype with the other 2. \r\n\r\nThe authors calculated the probability of the genotype-phenotype cosegragation occurring by chance (0.009) and this was lower than the recommended criterion (0.06) for strong evidence of pathogenicity.\r\n\r\nShared features included abnormal tone in most (hypotonia 6/8, limb hypertonia 1/8), seizures (8/8 - onset 2d - 7m), severe DD with speech delay/absent speech (8/8), ID (8/8), strabismus (6/8).\r\n\r\nUFSP2 encodes UFM1-specific protease 2 involved in UFmylation, a post-translational protein modification. As summarized by the authors the cysteine protease encoded by this gene (as is also the case for UFSP1) cleaves UFM1 in the initial step of UFMylation. Apart from producing mature UFM1, the 2 proteases have also the ability to release UFM1 from UFMylated proteins, in the process of de-UFMylation. [several refs. provided]\r\n\r\nUFMylation is important in brain development with mutations in genes encoding other components of the pathway reported in other NDD disorders (incl. UFM1, UBA5, UFC1).\r\n\r\nAdditional studies were carried to provide evidence for pathogenicity of this variant.\r\n\r\nSkin biopsies from 3 individuals were carried out to establish fibroblast cultures. Immunoblotting revealed reduced UFSP2 levels relative to controls. mRNA levels measured by qRT-PCR revealed no differences compared to controls altogether suggesting normal mRNA but reduced protein stability. \r\n\r\nThe authors demonstrated increased levels of UFM1-conjugated proteins (incl. DDRGK1, or TRIP4). Ectopic expression of wt UFSP2 normalized the levels of UFMylated proteins in the fibroblasts which was not the case for the V115E variant. Further the variant was difficult to detect by immunoblotting consistent with an effect on protein destabilization.\r\n\r\nAlthough disruption of UFMylation induces ER stress, this was not shown to occur in patient fibroblast lines, when assessed for ER stress markers.\r\n\r\nEvaluation of data from the GTEx project, concerning UFSP2 as well as well as DDRGK1 or TRIP4 - an UFMylation target - revealed relevant expression in multiple regions of the human brain.\r\n\r\nOverall the authors provide evidence for defective de-UFMylation in patient fibroblasts (presence of increased UFMylation marks). The authors stress out that the effect of the variant in UFMylation in brain is unknown, as UFSP1 or other enzymes might compensate in the presence of hypomorphic UFSP2 mutants.\r\n\r\n**Monoallelic** (correction to previous review) UFSP2 variants have previously been reported in 2 skeletal dysplasias [# 142669. BEUKES HIP DYSPLASIA; BHD and # 617974. SPONDYLOEPIMETAPHYSEAL DYSPLASIA, DI ROCCO TYPE; SEMDDR]. These disorders are not characterized by neurological dysfunction or epilepsy. The authors underscore the fact that variants identified in these disorders (Y290H, D526A, H428R) localize within the C-terminal catalytic (peptidase) domain [aa 278 – 461] while the variant here identified lies in the N-terminal substrate binding domain affecting protein stability/abundance.\r\n\r\nIn OMIM, only the 2 aforementioned disorders are currently associated with biallelic UFSP2 mutations. There is no associated phenotype in G2P. SysID includes UFSP2 among the primary ID genes.\r\n\r\nYou may consider inclusion in the current panel with amber/green rating. \r\nSources: Literature","entity_name":"UFSP2","entity_type":"gene"},{"created":"2021-05-26T04:31:04.426174+10:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.1085","user_name":"Konstantinos Varvagiannis","item_type":"entity","text":"changed review comment from: Ni et al (2021 - PMID: 33473208) describe the phenotype of 8 children (belonging to 4 families - 2 of which consanguineous) homozygous for a UFSP2 missense variant [NM_018359.5:c.344T>A; p.(Val115Glu)].\r\n\r\nMembers of a broader consanguineous pedigree from Pakistan with 3 affected children with epilepsy and DD and ID underwent exome sequencing. All affected individuals were homozygous for the specific SNV with their parents (2 parent pairs, in both cases first cousins) being heterozygous. An unaffected sib was homozygous for the wt allele. Through genematching platforms 3 additional families with similarly affected individuals and homozygosity for the same variant were recruited. These additional families were from Pakistan (1/3) and Afganistan (2/3). \r\n\r\nBased on ROH analysis from the broader first pedigree and an additional family the authors concluded on a single shared region of homozygosity on chr 4q. Lack of ES data did not allow verification of whether 2/4 families shared the same haplotype with the other 2. \r\n\r\nThe authors calculated the probability of the genotype-phenotype cosegragation occurring by chance (0.009) and this was lower than the recommended criterion (0.06) for strong evidence of pathogenicity.\r\n\r\nShared features included abnormal tone in most (hypotonia 6/8, limb hypertonia 1/8), seizures (8/8 - onset 2d - 7m), severe DD with speech delay/absent speech (8/8), ID (8/8), strabismus (6/8).\r\n\r\nUFSP2 encodes UFM1-specific protease 2 involved in UFmylation, a post-translational protein modification. As summarized by the authors the cysteine protease encoded by this gene (as is also the case for UFSP1) cleaves UFM1 in the initial step of UFMylation. Apart from producing mature UFM1, the 2 proteases have also the ability to release UFM1 from UFMylated proteins, in the process of de-UFMylation. [several refs. provided]\r\n\r\nUFMylation is important in brain development with mutations in genes encoding other components of the pathway reported in other NDD disorders (incl. UFM1, UBA5, UFC1).\r\n\r\nAdditional studies were carried to provide evidence for pathogenicity of this variant.\r\n\r\nSkin biopsies from 3 individuals were carried out to establish fibroblast cultures. Immunoblotting revealed reduced UFSP2 levels relative to controls. mRNA levels measured by qRT-PCR revealed no differences compared to controls altogether suggesting normal mRNA but reduced protein stability. \r\n\r\nThe authors demonstrated increased levels of UFM1-conjugated proteins (incl. DDRGK1, or TRIP4). Ectopic expression of wt UFSP2 normalized the levels of UFMylated proteins in the fibroblasts which was not the case for the V115E variant. Further the variant was difficult to detect by immunoblotting consistent with an effect on protein destabilization.\r\n\r\nAlthough disruption of UFMylation induces ER stress, this was not shown to occur in patient fibroblast lines, when assessed for ER stress markers.\r\n\r\nEvaluation of data from the GTEx project, concerning UFSP2 as well as well as DDRGK1 or TRIP4 - an UFMylation target - revealed relevant expression in multiple regions of the human brain.\r\n\r\nOverall the authors provide evidence for defective de-UFMylation in patient fibroblasts (presence of increased UFMylation marks). The authors stress out that the effect of the variant in UFMylation in brain is unknown, as UFSP1 or other enzymes might compensate in the presence of hypomorphic UFSP2 mutants.\r\n\r\nBiallelic UFSP2 variants have previously been reported in 2 skeletal dysplasias [# 142669. BEUKES HIP DYSPLASIA; BHD and # 617974. SPONDYLOEPIMETAPHYSEAL DYSPLASIA, DI ROCCO TYPE; SEMDDR]. These disorders are not characterized by neurological dysfunction or epilepsy. The authors underscore the fact that variants identified in these disorders (Y290H, D526A, H428R) localize within the C-terminal catalytic (peptidase) domain [aa 278 – 461] while the variant here identified lies in the N-terminal substrate binding domain affecting protein stability/abundance.\r\n\r\nIn OMIM, only the 2 aforementioned disorders are currently associated with biallelic UFSP2 mutations. There is no associated phenotype in G2P. SysID includes UFSP2 among the primary ID genes.\r\n\r\nYou may consider inclusion in the current panel with amber/green rating. \nSources: Literature; to: Ni et al (2021 - PMID: 33473208) describe the phenotype of 8 children (belonging to 4 families - 2 of which consanguineous) homozygous for a UFSP2 missense variant [NM_018359.5:c.344T>A; p.(Val115Glu)].\r\n\r\nMembers of a broader consanguineous pedigree from Pakistan with 3 affected children with epilepsy and DD and ID underwent exome sequencing. All affected individuals were homozygous for the specific SNV with their parents (2 parent pairs, in both cases first cousins) being heterozygous. An unaffected sib was homozygous for the wt allele. Through genematching platforms 3 additional families with similarly affected individuals and homozygosity for the same variant were recruited. These additional families were from Pakistan (1/3) and Afganistan (2/3). \r\n\r\nBased on ROH analysis from the broader first pedigree and an additional family the authors concluded on a single shared region of homozygosity on chr 4q. Lack of ES data did not allow verification of whether 2/4 families shared the same haplotype with the other 2. \r\n\r\nThe authors calculated the probability of the genotype-phenotype cosegragation occurring by chance (0.009) and this was lower than the recommended criterion (0.06) for strong evidence of pathogenicity.\r\n\r\nShared features included abnormal tone in most (hypotonia 6/8, limb hypertonia 1/8), seizures (8/8 - onset 2d - 7m), severe DD with speech delay/absent speech (8/8), ID (8/8), strabismus (6/8).\r\n\r\nUFSP2 encodes UFM1-specific protease 2 involved in UFmylation, a post-translational protein modification. As summarized by the authors the cysteine protease encoded by this gene (as is also the case for UFSP1) cleaves UFM1 in the initial step of UFMylation. Apart from producing mature UFM1, the 2 proteases have also the ability to release UFM1 from UFMylated proteins, in the process of de-UFMylation. [several refs. provided]\r\n\r\nUFMylation is important in brain development with mutations in genes encoding other components of the pathway reported in other NDD disorders (incl. UFM1, UBA5, UFC1).\r\n\r\nAdditional studies were carried to provide evidence for pathogenicity of this variant.\r\n\r\nSkin biopsies from 3 individuals were carried out to establish fibroblast cultures. Immunoblotting revealed reduced UFSP2 levels relative to controls. mRNA levels measured by qRT-PCR revealed no differences compared to controls altogether suggesting normal mRNA but reduced protein stability. \r\n\r\nThe authors demonstrated increased levels of UFM1-conjugated proteins (incl. DDRGK1, or TRIP4). Ectopic expression of wt UFSP2 normalized the levels of UFMylated proteins in the fibroblasts which was not the case for the V115E variant. Further the variant was difficult to detect by immunoblotting consistent with an effect on protein destabilization.\r\n\r\nAlthough disruption of UFMylation induces ER stress, this was not shown to occur in patient fibroblast lines, when assessed for ER stress markers.\r\n\r\nEvaluation of data from the GTEx project, concerning UFSP2 as well as well as DDRGK1 or TRIP4 - an UFMylation target - revealed relevant expression in multiple regions of the human brain.\r\n\r\nOverall the authors provide evidence for defective de-UFMylation in patient fibroblasts (presence of increased UFMylation marks). The authors stress out that the effect of the variant in UFMylation in brain is unknown, as UFSP1 or other enzymes might compensate in the presence of hypomorphic UFSP2 mutants.\r\n\r\n**Monoallelic** (correction to previous review) UFSP2 variants have previously been reported in 2 skeletal dysplasias [# 142669. BEUKES HIP DYSPLASIA; BHD and # 617974. SPONDYLOEPIMETAPHYSEAL DYSPLASIA, DI ROCCO TYPE; SEMDDR]. These disorders are not characterized by neurological dysfunction or epilepsy. The authors underscore the fact that variants identified in these disorders (Y290H, D526A, H428R) localize within the C-terminal catalytic (peptidase) domain [aa 278 – 461] while the variant here identified lies in the N-terminal substrate binding domain affecting protein stability/abundance.\r\n\r\nIn OMIM, only the 2 aforementioned disorders are currently associated with biallelic UFSP2 mutations. There is no associated phenotype in G2P. SysID includes UFSP2 among the primary ID genes.\r\n\r\nYou may consider inclusion in the current panel with amber/green rating. \r\nSources: Literature","entity_name":"UFSP2","entity_type":"gene"},{"created":"2021-05-25T20:55:01.650957+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.7675","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: DNAJB2 as ready","entity_name":"DNAJB2","entity_type":"gene"},{"created":"2021-05-25T20:55:01.632923+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.7675","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: dnajb2 has been classified as Green List (High Evidence).","entity_name":"DNAJB2","entity_type":"gene"},{"created":"2021-05-25T20:54:54.990921+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.7675","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: DNAJB2 were changed from  to Spinal muscular atrophy, distal, autosomal recessive, 5, MIM# 614881; MONDO:0014866","entity_name":"DNAJB2","entity_type":"gene"},{"created":"2021-05-25T20:54:38.109380+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.7674","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: DNAJB2 were set to ","entity_name":"DNAJB2","entity_type":"gene"},{"created":"2021-05-25T20:54:11.393782+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.7673","user_name":"Zornitza Stark","item_type":"entity","text":"Mode of inheritance for gene: DNAJB2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal","entity_name":"DNAJB2","entity_type":"gene"},{"created":"2021-05-25T20:53:52.005518+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.7672","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: DNAJB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22522442, 25274842, 33369814, 22522442; Phenotypes: Spinal muscular atrophy, distal, autosomal recessive, 5, MIM# 614881, MONDO:0014866; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"DNAJB2","entity_type":"gene"},{"created":"2021-05-25T20:44:39.130775+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.7672","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: ATP7A were changed from Occipital horn syndrome, 304150; X-linked recessive Menkes disease, 309400 Spinal muscular atrophy, distal, X-linked 3, 300489 to Menkes disease MIM#309400; Occipital horn syndrome MIM#304150; Spinal muscular atrophy, distal, X-linked 3, MIM# 300489","entity_name":"ATP7A","entity_type":"gene"},{"created":"2021-05-25T20:44:13.783986+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.7671","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: ATP7A were set to 21221114","entity_name":"ATP7A","entity_type":"gene"},{"created":"2021-05-25T20:43:41.708279+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.7670","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: ATP7A: Rating: GREEN; Mode of pathogenicity: None; Publications: 20170900, 33137485, 31969342, 31558336; Phenotypes: Menkes disease MIM#309400, Occipital horn syndrome MIM#304150, Spinal muscular atrophy, distal, X-linked 3, MIM# 300489; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females","entity_name":"ATP7A","entity_type":"gene"},{"created":"2021-05-25T19:54:09.918057+10:00","panel_name":"Skeletal dysplasia","panel_id":258,"panel_version":"0.102","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: UFSP2 as ready","entity_name":"UFSP2","entity_type":"gene"},{"created":"2021-05-25T19:54:09.908507+10:00","panel_name":"Skeletal dysplasia","panel_id":258,"panel_version":"0.102","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: ufsp2 has been classified as Amber List (Moderate Evidence).","entity_name":"UFSP2","entity_type":"gene"},{"created":"2021-05-25T19:54:05.177502+10:00","panel_name":"Skeletal dysplasia","panel_id":258,"panel_version":"0.102","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: UFSP2 were changed from Beukes Hip Dysplasia 142669, Spondyloepimetaphyseal dysplasia, Di Rocco type 617974 to Hip dysplasia, Beukes type, MIM#142669; Spondyloepimetaphyseal dysplasia, Di Rocco type, MIM# 617974","entity_name":"UFSP2","entity_type":"gene"},{"created":"2021-05-25T19:53:35.774972+10:00","panel_name":"Skeletal dysplasia","panel_id":258,"panel_version":"0.101","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: UFSP2 were set to 28892125; 26428751","entity_name":"UFSP2","entity_type":"gene"},{"created":"2021-05-25T19:52:55.180997+10:00","panel_name":"Skeletal dysplasia","panel_id":258,"panel_version":"0.100","user_name":"Zornitza Stark","item_type":"entity","text":"Mode of inheritance for gene: UFSP2 was changed from  to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted","entity_name":"UFSP2","entity_type":"gene"},{"created":"2021-05-25T19:52:24.165281+10:00","panel_name":"Skeletal dysplasia","panel_id":258,"panel_version":"0.99","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: UFSP2 as Amber List (moderate evidence)","entity_name":"UFSP2","entity_type":"gene"},{"created":"2021-05-25T19:52:24.154738+10:00","panel_name":"Skeletal dysplasia","panel_id":258,"panel_version":"0.99","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: ufsp2 has been classified as Amber List (Moderate Evidence).","entity_name":"UFSP2","entity_type":"gene"},{"created":"2021-05-25T19:51:59.355897+10:00","panel_name":"Skeletal dysplasia","panel_id":258,"panel_version":"0.98","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: UFSP2: Rating: AMBER; Mode of pathogenicity: None; Publications: 26428751, 28892125, 32755715; Phenotypes: Hip dysplasia, Beukes type, MIM#142669, Spondyloepimetaphyseal dysplasia, Di Rocco type, MIM# 617974; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted","entity_name":"UFSP2","entity_type":"gene"},{"created":"2021-05-25T19:50:49.295364+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.7670","user_name":"Zornitza Stark","item_type":"entity","text":"changed review comment from: Ni et al (2021 - PMID: 33473208) describe the phenotype of 8 children (belonging to 4 families - 2 of which consanguineous) homozygous for a UFSP2 missense variant [NM_018359.5:c.344T>A; p.(Val115Glu)]. Likely founder variant in all.\r\n\r\nHip dysplasia: single 8 generation family reported.\r\n\r\nSpondyloepimetaphyseal dysplasia, Di Rocco type: single 3-generation family reported.; to: Ni et al (2021 - PMID: 33473208) describe the phenotype of 8 children (belonging to 4 families - 2 of which consanguineous) homozygous for a UFSP2 missense variant [NM_018359.5:c.344T>A; p.(Val115Glu)]. Likely founder variant in all.\r\n\r\nHip dysplasia: single 8 generation family reported.\r\n\r\nSpondyloepimetaphyseal dysplasia, Di Rocco type: two families reported.","entity_name":"UFSP2","entity_type":"gene"},{"created":"2021-05-25T19:50:31.549041+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.7670","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: UFSP2: Changed publications: 33473208, 26428751, 28892125, 32755715","entity_name":"UFSP2","entity_type":"gene"},{"created":"2021-05-25T19:49:48.257855+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.7670","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: UFSP2: Rating: AMBER; Mode of pathogenicity: None; Publications: 33473208, 26428751, 28892125; Phenotypes: Neurodevelopmental disorder, Hip dysplasia, Beukes type, MIM#142669, Spondyloepimetaphyseal dysplasia, Di Rocco type, MIM# 617974; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal","entity_name":"UFSP2","entity_type":"gene"},{"created":"2021-05-25T19:46:08.275011+10:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.1085","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: UFSP2 as ready","entity_name":"UFSP2","entity_type":"gene"},{"created":"2021-05-25T19:46:08.255947+10:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.1085","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: ufsp2 has been classified as Amber List (Moderate Evidence).","entity_name":"UFSP2","entity_type":"gene"},{"created":"2021-05-25T19:46:00.771593+10:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.1085","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: UFSP2 as Amber List (moderate evidence)","entity_name":"UFSP2","entity_type":"gene"},{"created":"2021-05-25T19:46:00.762694+10:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.1085","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: ufsp2 has been classified as Amber List (Moderate Evidence).","entity_name":"UFSP2","entity_type":"gene"},{"created":"2021-05-25T19:45:30.693942+10:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.1084","user_name":"Zornitza Stark","item_type":"entity","text":"Tag founder tag was added to gene: UFSP2.","entity_name":"UFSP2","entity_type":"gene"},{"created":"2021-05-25T19:43:01.787958+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3786","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: UFSP2 as ready","entity_name":"UFSP2","entity_type":"gene"},{"created":"2021-05-25T19:43:01.783209+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3786","user_name":"Zornitza Stark","item_type":"entity","text":"Added comment: Comment when marking as ready: Amber rating as single, likely founder variant.","entity_name":"UFSP2","entity_type":"gene"},{"created":"2021-05-25T19:43:01.750583+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3786","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: ufsp2 has been classified as Amber List (Moderate Evidence).","entity_name":"UFSP2","entity_type":"gene"},{"created":"2021-05-25T19:42:55.839450+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3786","user_name":"Zornitza Stark","item_type":"entity","text":"Tag founder tag was added to gene: UFSP2.","entity_name":"UFSP2","entity_type":"gene"},{"created":"2021-05-25T19:42:23.129515+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3786","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: UFSP2 as Amber List (moderate evidence)","entity_name":"UFSP2","entity_type":"gene"},{"created":"2021-05-25T19:42:23.118385+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3786","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: ufsp2 has been classified as Amber List (Moderate Evidence).","entity_name":"UFSP2","entity_type":"gene"},{"created":"2021-05-25T08:20:54.673729+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.7670","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: TRPV6 as ready","entity_name":"TRPV6","entity_type":"gene"},{"created":"2021-05-25T08:20:54.665062+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.7670","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: trpv6 has been classified as Green List (High Evidence).","entity_name":"TRPV6","entity_type":"gene"},{"created":"2021-05-25T08:20:47.028090+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.7670","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: TRPV6 were changed from  to Hyperparathyroidism, transient neonatal, MIM# 618188; Early onset chronic pancreatitis susceptibility","entity_name":"TRPV6","entity_type":"gene"},{"created":"2021-05-25T08:20:26.943887+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.7669","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: TRPV6 were set to ","entity_name":"TRPV6","entity_type":"gene"},{"created":"2021-05-25T08:20:07.949968+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.7668","user_name":"Zornitza Stark","item_type":"entity","text":"Mode of inheritance for gene: TRPV6 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal","entity_name":"TRPV6","entity_type":"gene"},{"created":"2021-05-25T08:19:49.842871+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.7667","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: TRPV6: Rating: GREEN; Mode of pathogenicity: None; Publications: 32383311, 31930989, 29861107; Phenotypes: Hyperparathyroidism, transient neonatal, MIM# 618188, Early onset chronic pancreatitis susceptibility; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal","entity_name":"TRPV6","entity_type":"gene"},{"created":"2021-05-24T04:29:10.218711+10:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"0.1084","user_name":"Konstantinos Varvagiannis","item_type":"entity","text":"gene: UFSP2 was added\ngene: UFSP2 was added to Genetic Epilepsy. Sources: Literature\nMode of inheritance for gene: UFSP2 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: UFSP2 were set to 33473208\nPhenotypes for gene: UFSP2 were set to Abnormal muscle tone; Seizures; Global developmental delay; Delayed speech and language development; Intellectual disability; Strabismus\nPenetrance for gene: UFSP2 were set to Complete\nReview for gene: UFSP2 was set to AMBER\nAdded comment: Ni et al (2021 - PMID: 33473208) describe the phenotype of 8 children (belonging to 4 families - 2 of which consanguineous) homozygous for a UFSP2 missense variant [NM_018359.5:c.344T>A; p.(Val115Glu)].\r\n\r\nMembers of a broader consanguineous pedigree from Pakistan with 3 affected children with epilepsy and DD and ID underwent exome sequencing. All affected individuals were homozygous for the specific SNV with their parents (2 parent pairs, in both cases first cousins) being heterozygous. An unaffected sib was homozygous for the wt allele. Through genematching platforms 3 additional families with similarly affected individuals and homozygosity for the same variant were recruited. These additional families were from Pakistan (1/3) and Afganistan (2/3). \r\n\r\nBased on ROH analysis from the broader first pedigree and an additional family the authors concluded on a single shared region of homozygosity on chr 4q. Lack of ES data did not allow verification of whether 2/4 families shared the same haplotype with the other 2. \r\n\r\nThe authors calculated the probability of the genotype-phenotype cosegragation occurring by chance (0.009) and this was lower than the recommended criterion (0.06) for strong evidence of pathogenicity.\r\n\r\nShared features included abnormal tone in most (hypotonia 6/8, limb hypertonia 1/8), seizures (8/8 - onset 2d - 7m), severe DD with speech delay/absent speech (8/8), ID (8/8), strabismus (6/8).\r\n\r\nUFSP2 encodes UFM1-specific protease 2 involved in UFmylation, a post-translational protein modification. As summarized by the authors the cysteine protease encoded by this gene (as is also the case for UFSP1) cleaves UFM1 in the initial step of UFMylation. Apart from producing mature UFM1, the 2 proteases have also the ability to release UFM1 from UFMylated proteins, in the process of de-UFMylation. [several refs. provided]\r\n\r\nUFMylation is important in brain development with mutations in genes encoding other components of the pathway reported in other NDD disorders (incl. UFM1, UBA5, UFC1).\r\n\r\nAdditional studies were carried to provide evidence for pathogenicity of this variant.\r\n\r\nSkin biopsies from 3 individuals were carried out to establish fibroblast cultures. Immunoblotting revealed reduced UFSP2 levels relative to controls. mRNA levels measured by qRT-PCR revealed no differences compared to controls altogether suggesting normal mRNA but reduced protein stability. \r\n\r\nThe authors demonstrated increased levels of UFM1-conjugated proteins (incl. DDRGK1, or TRIP4). Ectopic expression of wt UFSP2 normalized the levels of UFMylated proteins in the fibroblasts which was not the case for the V115E variant. Further the variant was difficult to detect by immunoblotting consistent with an effect on protein destabilization.\r\n\r\nAlthough disruption of UFMylation induces ER stress, this was not shown to occur in patient fibroblast lines, when assessed for ER stress markers.\r\n\r\nEvaluation of data from the GTEx project, concerning UFSP2 as well as well as DDRGK1 or TRIP4 - an UFMylation target - revealed relevant expression in multiple regions of the human brain.\r\n\r\nOverall the authors provide evidence for defective de-UFMylation in patient fibroblasts (presence of increased UFMylation marks). The authors stress out that the effect of the variant in UFMylation in brain is unknown, as UFSP1 or other enzymes might compensate in the presence of hypomorphic UFSP2 mutants.\r\n\r\nBiallelic UFSP2 variants have previously been reported in 2 skeletal dysplasias [# 142669. BEUKES HIP DYSPLASIA; BHD and # 617974. SPONDYLOEPIMETAPHYSEAL DYSPLASIA, DI ROCCO TYPE; SEMDDR]. These disorders are not characterized by neurological dysfunction or epilepsy. The authors underscore the fact that variants identified in these disorders (Y290H, D526A, H428R) localize within the C-terminal catalytic (peptidase) domain [aa 278 – 461] while the variant here identified lies in the N-terminal substrate binding domain affecting protein stability/abundance.\r\n\r\nIn OMIM, only the 2 aforementioned disorders are currently associated with biallelic UFSP2 mutations. There is no associated phenotype in G2P. SysID includes UFSP2 among the primary ID genes.\r\n\r\nYou may consider inclusion in the current panel with amber/green rating. \nSources: Literature","entity_name":"UFSP2","entity_type":"gene"},{"created":"2021-05-24T04:29:08.413578+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3785","user_name":"Konstantinos Varvagiannis","item_type":"entity","text":"gene: UFSP2 was added\ngene: UFSP2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature\nMode of inheritance for gene: UFSP2 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: UFSP2 were set to 33473208\nPhenotypes for gene: UFSP2 were set to Abnormal muscle tone; Seizures; Global developmental delay; Delayed speech and language development; Intellectual disability; Strabismus\nPenetrance for gene: UFSP2 were set to Complete\nReview for gene: UFSP2 was set to AMBER\nAdded comment: Ni et al (2021 - PMID: 33473208) describe the phenotype of 8 children (belonging to 4 families - 2 of which consanguineous) homozygous for a UFSP2 missense variant [NM_018359.5:c.344T>A; p.(Val115Glu)].\r\n\r\nMembers of a broader consanguineous pedigree from Pakistan with 3 affected children with epilepsy and DD and ID underwent exome sequencing. All affected individuals were homozygous for the specific SNV with their parents (2 parent pairs, in both cases first cousins) being heterozygous. An unaffected sib was homozygous for the wt allele. Through genematching platforms 3 additional families with similarly affected individuals and homozygosity for the same variant were recruited. These additional families were from Pakistan (1/3) and Afganistan (2/3). \r\n\r\nBased on ROH analysis from the broader first pedigree and an additional family the authors concluded on a single shared region of homozygosity on chr 4q. Lack of ES data did not allow verification of whether 2/4 families shared the same haplotype with the other 2. \r\n\r\nThe authors calculated the probability of the genotype-phenotype cosegragation occurring by chance (0.009) and this was lower than the recommended criterion (0.06) for strong evidence of pathogenicity.\r\n\r\nShared features included abnormal tone in most (hypotonia 6/8, limb hypertonia 1/8), seizures (8/8 - onset 2d - 7m), severe DD with speech delay/absent speech (8/8), ID (8/8), strabismus (6/8).\r\n\r\nUFSP2 encodes UFM1-specific protease 2 involved in UFmylation, a post-translational protein modification. As summarized by the authors the cysteine protease encoded by this gene (as is also the case for UFSP1) cleaves UFM1 in the initial step of UFMylation. Apart from producing mature UFM1, the 2 proteases have also the ability to release UFM1 from UFMylated proteins, in the process of de-UFMylation. [several refs. provided]\r\n\r\nUFMylation is important in brain development with mutations in genes encoding other components of the pathway reported in other NDD disorders (incl. UFM1, UBA5, UFC1).\r\n\r\nAdditional studies were carried to provide evidence for pathogenicity of this variant.\r\n\r\nSkin biopsies from 3 individuals were carried out to establish fibroblast cultures. Immunoblotting revealed reduced UFSP2 levels relative to controls. mRNA levels measured by qRT-PCR revealed no differences compared to controls altogether suggesting normal mRNA but reduced protein stability. \r\n\r\nThe authors demonstrated increased levels of UFM1-conjugated proteins (incl. DDRGK1, or TRIP4). Ectopic expression of wt UFSP2 normalized the levels of UFMylated proteins in the fibroblasts which was not the case for the V115E variant. Further the variant was difficult to detect by immunoblotting consistent with an effect on protein destabilization.\r\n\r\nAlthough disruption of UFMylation induces ER stress, this was not shown to occur in patient fibroblast lines, when assessed for ER stress markers.\r\n\r\nEvaluation of data from the GTEx project, concerning UFSP2 as well as well as DDRGK1 or TRIP4 - an UFMylation target - revealed relevant expression in multiple regions of the human brain.\r\n\r\nOverall the authors provide evidence for defective de-UFMylation in patient fibroblasts (presence of increased UFMylation marks). The authors stress out that the effect of the variant in UFMylation in brain is unknown, as UFSP1 or other enzymes might compensate in the presence of hypomorphic UFSP2 mutants.\r\n\r\nBiallelic UFSP2 variants have previously been reported in 2 skeletal dysplasias [# 142669. BEUKES HIP DYSPLASIA; BHD and # 617974. SPONDYLOEPIMETAPHYSEAL DYSPLASIA, DI ROCCO TYPE; SEMDDR]. These disorders are not characterized by neurological dysfunction or epilepsy. The authors underscore the fact that variants identified in these disorders (Y290H, D526A, H428R) localize within the C-terminal catalytic (peptidase) domain [aa 278 – 461] while the variant here identified lies in the N-terminal substrate binding domain affecting protein stability/abundance.\r\n\r\nIn OMIM, only the 2 aforementioned disorders are currently associated with biallelic UFSP2 mutations. There is no associated phenotype in G2P. SysID includes UFSP2 among the primary ID genes.\r\n\r\nYou may consider inclusion in the current panel with amber/green rating. \nSources: Literature","entity_name":"UFSP2","entity_type":"gene"},{"created":"2021-05-23T19:06:08.923981+10:00","panel_name":"Hereditary Spastic Paraplegia - paediatric","panel_id":317,"panel_version":"1.13","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: FAR1 were changed from spastic paraparesis and bilateral cataracts; Peroxisomal fatty acyl-CoA reductase 1 disorder, MIM#\t616154 to Cataracts, spastic paraparesis, and speech delay, MIM#619338; Peroxisomal fatty acyl-CoA reductase 1 disorder, MIM#\t616154","entity_name":"FAR1","entity_type":"gene"},{"created":"2021-05-23T19:05:52.850794+10:00","panel_name":"Hereditary Spastic Paraplegia - paediatric","panel_id":317,"panel_version":"1.12","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: FAR1: Changed rating: GREEN; Changed phenotypes: Cataracts, spastic paraparesis, and speech delay, MIM#619338; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted","entity_name":"FAR1","entity_type":"gene"},{"created":"2021-05-23T19:05:32.890171+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3785","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: FAR1 were changed from Peroxisomal fatty acyl-CoA reductase 1 disorder, MIM#616154; 33239752 to Peroxisomal fatty acyl-CoA reductase 1 disorder, MIM#616154; Cataracts, spastic paraparesis, and speech delay, MIM#619338","entity_name":"FAR1","entity_type":"gene"},{"created":"2021-05-23T19:04:52.158491+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3784","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: FAR1: Changed phenotypes: Peroxisomal fatty acyl-CoA reductase 1 disorder, MIM#616154, Cataracts, spastic paraparesis, and speech delay, MIM#619338","entity_name":"FAR1","entity_type":"gene"},{"created":"2021-05-23T19:04:31.403542+10:00","panel_name":"Peroxisomal Disorders","panel_id":155,"panel_version":"0.20","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: FAR1 were changed from Peroxisomal fatty acyl-CoA reductase 1 disorder (MIM#616154); spastic paraparesis and bilateral cataracts to Peroxisomal fatty acyl-CoA reductase 1 disorder (MIM#616154); Cataracts, spastic paraparesis, and speech delay, MIM#619338","entity_name":"FAR1","entity_type":"gene"},{"created":"2021-05-23T19:03:54.271426+10:00","panel_name":"Peroxisomal Disorders","panel_id":155,"panel_version":"0.19","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: FAR1: Changed phenotypes: Cataracts, spastic paraparesis, and speech delay, MIM#619338","entity_name":"FAR1","entity_type":"gene"},{"created":"2021-05-23T19:03:34.458790+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.7667","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: FAR1 were changed from Peroxisomal fatty acyl-CoA reductase 1 disorder, MIM#616154; spastic paraparesis and bilateral cataracts to Peroxisomal fatty acyl-CoA reductase 1 disorder, MIM#616154; Cataracts, spastic paraparesis, and speech delay, MIM#619338","entity_name":"FAR1","entity_type":"gene"},{"created":"2021-05-23T19:03:15.757587+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.7666","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: FAR1: Changed phenotypes: Peroxisomal fatty acyl-CoA reductase 1 disorder, MIM#616154, Cataracts, spastic paraparesis, and speech delay, MIM#619338","entity_name":"FAR1","entity_type":"gene"},{"created":"2021-05-23T19:02:57.382109+10:00","panel_name":"Cataract","panel_id":66,"panel_version":"0.277","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: FAR1 were changed from spastic paraparesis and bilateral cataracts; Peroxisomal fatty acyl-CoA reductase 1 disorder, MIM# 616154 to Cataracts, spastic paraparesis, and speech delay, MIM#619338; Peroxisomal fatty acyl-CoA reductase 1 disorder, MIM# 616154","entity_name":"FAR1","entity_type":"gene"},{"created":"2021-05-23T19:02:13.675360+10:00","panel_name":"Cataract","panel_id":66,"panel_version":"0.276","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: FAR1: Changed phenotypes: Peroxisomal fatty acyl-CoA reductase 1 disorder, MIM# 616154, Cataracts, spastic paraparesis, and speech delay, MIM#619338","entity_name":"FAR1","entity_type":"gene"},{"created":"2021-05-23T19:01:08.914837+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.7666","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: CLDN11 were changed from Hypomyelinating leukodystrophy to Hypomyelinating leukodystrophy-22, MIM#619328","entity_name":"CLDN11","entity_type":"gene"},{"created":"2021-05-23T19:00:47.869101+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.7665","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: CLDN11: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypomyelinating leukodystrophy-22, MIM#619328; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted","entity_name":"CLDN11","entity_type":"gene"},{"created":"2021-05-23T19:00:05.520782+10:00","panel_name":"Leukodystrophy - paediatric","panel_id":298,"panel_version":"0.222","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: CLDN11 were changed from Hypomyelinating leukodystrophy to Hypomyelinating leukodystrophy-22, MIM#619328","entity_name":"CLDN11","entity_type":"gene"},{"created":"2021-05-23T18:59:45.913236+10:00","panel_name":"Leukodystrophy - paediatric","panel_id":298,"panel_version":"0.221","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: CLDN11: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypomyelinating leukodystrophy-22, MIM#619328; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted","entity_name":"CLDN11","entity_type":"gene"},{"created":"2021-05-23T18:58:37.065391+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3784","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: BICRA were changed from Developmental delay, intellectual disability, autism spectrum disorder,behavioral abnormalities, dysmorphic features to Coffin-Siris syndrome-12, MIM#619325; Developmental delay, intellectual disability, autism spectrum disorder,behavioral abnormalities, dysmorphic features","entity_name":"BICRA","entity_type":"gene"},{"created":"2021-05-23T18:58:07.845602+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.3783","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: BICRA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Coffin-Siris syndrome-12, MIM#619325; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted","entity_name":"BICRA","entity_type":"gene"},{"created":"2021-05-23T18:57:48.519688+10:00","panel_name":"Autism","panel_id":51,"panel_version":"0.142","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: BICRA were changed from Developmental delay, intellectual disability, autism spectrum disorder,behavioral abnormalities, dysmorphic features to Coffin-Siris syndrome-12, MIM#619325; Developmental delay, intellectual disability, autism spectrum disorder,behavioral abnormalities, dysmorphic features","entity_name":"BICRA","entity_type":"gene"},{"created":"2021-05-23T18:57:16.725722+10:00","panel_name":"Autism","panel_id":51,"panel_version":"0.141","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: BICRA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Coffin-Siris syndrome-12, MIM#619325; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted","entity_name":"BICRA","entity_type":"gene"},{"created":"2021-05-23T18:56:41.826851+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.7665","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: BICRA were changed from Developmental delay, intellectual disability, autism spectrum disorder,behavioral abnormalities, dysmorphic features to Coffin-Siris syndrome-12, MIM#619325; Developmental delay, intellectual disability, autism spectrum disorder,behavioral abnormalities, dysmorphic features","entity_name":"BICRA","entity_type":"gene"},{"created":"2021-05-23T18:56:07.668867+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.7664","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: BICRA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Coffin-Siris syndrome-12, MIM#619325; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted","entity_name":"BICRA","entity_type":"gene"},{"created":"2021-05-22T17:20:50.140085+10:00","panel_name":"Incidentalome","panel_id":126,"panel_version":"0.67","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: MBD4 as ready","entity_name":"MBD4","entity_type":"gene"},{"created":"2021-05-22T17:20:50.127396+10:00","panel_name":"Incidentalome","panel_id":126,"panel_version":"0.67","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: mbd4 has been classified as Amber List (Moderate Evidence).","entity_name":"MBD4","entity_type":"gene"},{"created":"2021-05-22T17:20:42.011318+10:00","panel_name":"Incidentalome","panel_id":126,"panel_version":"0.67","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: MBD4 as Amber List (moderate evidence)","entity_name":"MBD4","entity_type":"gene"},{"created":"2021-05-22T17:20:42.001198+10:00","panel_name":"Incidentalome","panel_id":126,"panel_version":"0.67","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: mbd4 has been classified as Amber List (Moderate Evidence).","entity_name":"MBD4","entity_type":"gene"},{"created":"2021-05-22T17:20:07.407594+10:00","panel_name":"Incidentalome","panel_id":126,"panel_version":"0.66","user_name":"Zornitza Stark","item_type":"entity","text":"gene: MBD4 was added\ngene: MBD4 was added to Incidentalome. Sources: Literature\nMode of inheritance for gene: MBD4 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: MBD4 were set to https://www.biorxiv.org/content/10.1101/2021.04.27.441137v1.full.pdf\nPhenotypes for gene: MBD4 were set to AML and colorectal polyps; MBD4-associated neoplasia syndrome\nReview for gene: MBD4 was set to AMBER\nAdded comment: Three individuals reported with bi-allelic LOF and rare combination of AML and adenomatous colorectal polyps. \nSources: Literature","entity_name":"MBD4","entity_type":"gene"},{"created":"2021-05-21T20:59:00.688012+10:00","panel_name":"Autonomic neuropathy","panel_id":3439,"panel_version":"0.48","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: RETREG1 were changed from OMIM# 613115 NEUROPATHY, HEREDITARY SENSORY AND AUTONOMIC, TYPE IIB; HSAN2B to Neuropathy, hereditary sensory and autonomic, type IIB, MIM# 613115; MONDO:0013142","entity_name":"RETREG1","entity_type":"gene"},{"created":"2021-05-21T20:58:50.967676+10:00","panel_name":"Autonomic neuropathy","panel_id":3439,"panel_version":"0.47","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: RETREG1 were set to ","entity_name":"RETREG1","entity_type":"gene"},{"created":"2021-05-21T20:58:34.436462+10:00","panel_name":"Autonomic neuropathy","panel_id":3439,"panel_version":"0.46","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: RETREG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19838196, 24327336, 31737055, 31596031; Phenotypes: Neuropathy, hereditary sensory and autonomic, type IIB, MIM# 613115, MONDO:0013142; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"RETREG1","entity_type":"gene"},{"created":"2021-05-21T20:57:16.376811+10:00","panel_name":"Additional findings_Paediatric","panel_id":3302,"panel_version":"0.220","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: RETREG1 as ready","entity_name":"RETREG1","entity_type":"gene"},{"created":"2021-05-21T20:57:16.361256+10:00","panel_name":"Additional findings_Paediatric","panel_id":3302,"panel_version":"0.220","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: retreg1 has been classified as Green List (High Evidence).","entity_name":"RETREG1","entity_type":"gene"},{"created":"2021-05-21T20:57:12.718775+10:00","panel_name":"Additional findings_Paediatric","panel_id":3302,"panel_version":"0.220","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: RETREG1 were changed from Neuropathy, hereditary sensory and autonomic, type IIB to Neuropathy, hereditary sensory and autonomic, type IIB, MIM# 613115; MONDO:0013142","entity_name":"RETREG1","entity_type":"gene"},{"created":"2021-05-21T20:56:57.605068+10:00","panel_name":"Additional findings_Paediatric","panel_id":3302,"panel_version":"0.219","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: RETREG1 were set to ","entity_name":"RETREG1","entity_type":"gene"},{"created":"2021-05-21T20:56:42.844823+10:00","panel_name":"Additional findings_Paediatric","panel_id":3302,"panel_version":"0.218","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: RETREG1 as Green List (high evidence)","entity_name":"RETREG1","entity_type":"gene"},{"created":"2021-05-21T20:56:42.835504+10:00","panel_name":"Additional findings_Paediatric","panel_id":3302,"panel_version":"0.218","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: retreg1 has been classified as Green List (High Evidence).","entity_name":"RETREG1","entity_type":"gene"},{"created":"2021-05-21T20:56:28.283590+10:00","panel_name":"Additional findings_Paediatric","panel_id":3302,"panel_version":"0.217","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: RETREG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19838196, 24327336, 31737055, 31596031; Phenotypes: Neuropathy, hereditary sensory and autonomic, type IIB, MIM# 613115, MONDO:0013142; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"RETREG1","entity_type":"gene"},{"created":"2021-05-21T20:55:44.112945+10:00","panel_name":"Pain syndromes","panel_id":3126,"panel_version":"0.26","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: RETREG1 as ready","entity_name":"RETREG1","entity_type":"gene"},{"created":"2021-05-21T20:55:44.096427+10:00","panel_name":"Pain syndromes","panel_id":3126,"panel_version":"0.26","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: retreg1 has been classified as Green List (High Evidence).","entity_name":"RETREG1","entity_type":"gene"},{"created":"2021-05-21T20:55:37.695784+10:00","panel_name":"Pain syndromes","panel_id":3126,"panel_version":"0.26","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: RETREG1 were changed from Hereditary sensory and autonomic neuropathy; Neuropathy, hereditary sensory and autonomic, type IIB, 613115; HSAN 2B to Neuropathy, hereditary sensory and autonomic, type IIB, MIM# 613115; MONDO:0013142","entity_name":"RETREG1","entity_type":"gene"},{"created":"2021-05-21T20:55:24.422791+10:00","panel_name":"Pain syndromes","panel_id":3126,"panel_version":"0.25","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: RETREG1 were set to 19838196; 21115472; 24327336","entity_name":"RETREG1","entity_type":"gene"},{"created":"2021-05-21T20:55:03.477055+10:00","panel_name":"Pain syndromes","panel_id":3126,"panel_version":"0.24","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: RETREG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19838196, 24327336, 31737055, 31596031; Phenotypes: Neuropathy, hereditary sensory and autonomic, type IIB, MIM# 613115, MONDO:0013142; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"RETREG1","entity_type":"gene"},{"created":"2021-05-21T20:54:19.253564+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.7664","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: RETREG1 as ready","entity_name":"RETREG1","entity_type":"gene"},{"created":"2021-05-21T20:54:19.244313+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.7664","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: retreg1 has been classified as Green List (High Evidence).","entity_name":"RETREG1","entity_type":"gene"},{"created":"2021-05-21T20:54:11.393736+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.7664","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: RETREG1 were changed from  to Neuropathy, hereditary sensory and autonomic, type IIB, MIM# 613115; MONDO:0013142","entity_name":"RETREG1","entity_type":"gene"},{"created":"2021-05-21T20:53:55.064789+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.7663","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: RETREG1 were set to ","entity_name":"RETREG1","entity_type":"gene"},{"created":"2021-05-21T20:53:34.109712+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.7662","user_name":"Zornitza Stark","item_type":"entity","text":"Mode of inheritance for gene: RETREG1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal","entity_name":"RETREG1","entity_type":"gene"},{"created":"2021-05-21T20:53:15.980878+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.7661","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: RETREG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19838196, 24327336, 31737055, 31596031; Phenotypes: Neuropathy, hereditary sensory and autonomic, type IIB, MIM# 613115, MONDO:0013142; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"RETREG1","entity_type":"gene"}]}