{"count":220842,"next":"https://panelapp-aus.org/api/v1/activities/?format=json&page=1238","previous":"https://panelapp-aus.org/api/v1/activities/?format=json&page=1236","results":[{"created":"2021-08-15T14:29:21.822974+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.120","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: ANAPC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31303264; Phenotypes: Rothmund-Thomson syndrome, type 1, MIM# 618625; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"ANAPC1","entity_type":"gene"},{"created":"2021-08-15T14:25:03.348965+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.120","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: FANCM as ready","entity_name":"FANCM","entity_type":"gene"},{"created":"2021-08-15T14:25:03.338701+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.120","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: fancm has been classified as Red List (Low Evidence).","entity_name":"FANCM","entity_type":"gene"},{"created":"2021-08-15T14:25:00.556245+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.120","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: FANCM were changed from Fanconi anemia, complementation group M, 614087; Fanconi anemia; Fanconi Anemia to Fanconi anaemia","entity_name":"FANCM","entity_type":"gene"},{"created":"2021-08-15T14:24:26.360596+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.119","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: SMC3 as ready","entity_name":"SMC3","entity_type":"gene"},{"created":"2021-08-15T14:24:26.351635+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.119","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: smc3 has been classified as Green List (High Evidence).","entity_name":"SMC3","entity_type":"gene"},{"created":"2021-08-15T14:24:24.130183+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.119","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: SMC3 were changed from Cornelia De Lange to Cornelia de Lange syndrome 3, MIM# 610759","entity_name":"SMC3","entity_type":"gene"},{"created":"2021-08-15T14:24:16.196434+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.118","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: SMC3 were set to ","entity_name":"SMC3","entity_type":"gene"},{"created":"2021-08-15T14:23:50.442995+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.117","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: SMC3 as Green List (high evidence)","entity_name":"SMC3","entity_type":"gene"},{"created":"2021-08-15T14:23:50.432476+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.117","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: smc3 has been classified as Green List (High Evidence).","entity_name":"SMC3","entity_type":"gene"},{"created":"2021-08-15T14:23:42.359037+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.116","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: SMC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 25125236, 25655089; Phenotypes: Cornelia de Lange syndrome 3, MIM# 610759; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted","entity_name":"SMC3","entity_type":"gene"},{"created":"2021-08-15T14:21:51.741024+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.116","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: SOX3 as ready","entity_name":"SOX3","entity_type":"gene"},{"created":"2021-08-15T14:21:51.732129+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.116","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: sox3 has been classified as Red List (Low Evidence).","entity_name":"SOX3","entity_type":"gene"},{"created":"2021-08-15T14:21:49.179347+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.116","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: SOX3 were changed from Panhypopituitarism, X-linked, OMIM:312000; Mental retardation, X-linked, with isolated growth hormone deficiency, OMIM:300123; Panhypopituitarism, X-linked, MONDO:0010712; Intellectual disability, X-linked, with panhypopituitarism, MONDO:0010252 to Mental retardation, X-linked, with isolated growth hormone deficiency, MIM#300123; Panhypopituitarism, X-linked, MIM#312000","entity_name":"SOX3","entity_type":"gene"},{"created":"2021-08-15T14:21:33.567849+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.115","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: SOX3 were set to 15800844","entity_name":"SOX3","entity_type":"gene"},{"created":"2021-08-15T14:21:21.780599+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.114","user_name":"Zornitza Stark","item_type":"entity","text":"Mode of inheritance for gene: SOX3 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, biallelic mutations in females","entity_name":"SOX3","entity_type":"gene"},{"created":"2021-08-15T14:21:14.292136+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.113","user_name":"Zornitza Stark","item_type":"entity","text":"Tag SV/CNV tag was added to gene: SOX3.","entity_name":"SOX3","entity_type":"gene"},{"created":"2021-08-15T14:21:05.501360+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.113","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: SOX3: Rating: RED; Mode of pathogenicity: None; Publications: 29175558, 30125608, 12428212, 15800844; Phenotypes: Mental retardation, X-linked, with isolated growth hormone deficiency, MIM#300123, Panhypopituitarism, X-linked, MIM#312000; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females","entity_name":"SOX3","entity_type":"gene"},{"created":"2021-08-15T12:56:35.252259+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.113","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: SOX2 as ready","entity_name":"SOX2","entity_type":"gene"},{"created":"2021-08-15T12:56:35.242462+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.113","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: sox2 has been classified as Green List (High Evidence).","entity_name":"SOX2","entity_type":"gene"},{"created":"2021-08-15T12:56:32.422843+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.113","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: SOX2 were changed from  to Microphthalmia, syndromic 3, MIM# 206900","entity_name":"SOX2","entity_type":"gene"},{"created":"2021-08-15T12:56:26.168597+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.112","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: SOX2 were set to ","entity_name":"SOX2","entity_type":"gene"},{"created":"2021-08-15T12:56:17.364007+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.111","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: SOX2 as Green List (high evidence)","entity_name":"SOX2","entity_type":"gene"},{"created":"2021-08-15T12:56:17.354641+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.111","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: sox2 has been classified as Green List (High Evidence).","entity_name":"SOX2","entity_type":"gene"},{"created":"2021-08-15T12:56:08.615496+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.110","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: SOX2: Rating: GREEN; Mode of pathogenicity: None; Publications: 15812812, 16543359, 16932809,; Phenotypes: Microphthalmia, syndromic 3, MIM# 206900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted","entity_name":"SOX2","entity_type":"gene"},{"created":"2021-08-15T12:53:56.006781+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.110","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: ERCC8: Changed phenotypes: Cockayne syndrome, type A, MIM# 216400, MONDO:0019569","entity_name":"ERCC8","entity_type":"gene"},{"created":"2021-08-15T12:53:45.489124+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.110","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: ERCC8 as ready","entity_name":"ERCC8","entity_type":"gene"},{"created":"2021-08-15T12:53:45.478299+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.110","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: ercc8 has been classified as Green List (High Evidence).","entity_name":"ERCC8","entity_type":"gene"},{"created":"2021-08-15T12:53:43.415664+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.110","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: ERCC8 were changed from cockayne to Cockayne syndrome, type A, MIM# 216400; MONDO:0019569","entity_name":"ERCC8","entity_type":"gene"},{"created":"2021-08-15T12:53:33.783129+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.109","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: ERCC8 were set to ","entity_name":"ERCC8","entity_type":"gene"},{"created":"2021-08-15T12:53:25.751276+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.108","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: ERCC8 as Green List (high evidence)","entity_name":"ERCC8","entity_type":"gene"},{"created":"2021-08-15T12:53:25.741646+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.108","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: ercc8 has been classified as Green List (High Evidence).","entity_name":"ERCC8","entity_type":"gene"},{"created":"2021-08-15T12:53:08.089176+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.107","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: ERCC6 as ready","entity_name":"ERCC6","entity_type":"gene"},{"created":"2021-08-15T12:53:08.079014+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.107","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: ercc6 has been classified as Green List (High Evidence).","entity_name":"ERCC6","entity_type":"gene"},{"created":"2021-08-15T12:53:05.797967+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.107","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: ERCC6 were changed from Cockayne syndrome, type B, 133540 to Cerebrooculofacioskeletal syndrome 1, MIM# 214150; MONDO:0008955; Cockayne syndrome, type B, MIM# 133540; MONDO:0019570","entity_name":"ERCC6","entity_type":"gene"},{"created":"2021-08-15T12:52:54.169655+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.106","user_name":"Zornitza Stark","item_type":"entity","text":"changed review comment from: Well established gene-disease association, spectrum of severity.; to: Well established gene-disease association, spectrum of severity. Marked short stature is a feature.","entity_name":"ERCC6","entity_type":"gene"},{"created":"2021-08-15T12:52:42.018773+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.106","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: ERCC6: Changed phenotypes: Cerebrooculofacioskeletal syndrome 1, MIM# 214150, MONDO:0008955, Cockayne syndrome, type B, MIM# 133540, MONDO:0019570","entity_name":"ERCC6","entity_type":"gene"},{"created":"2021-08-15T12:52:07.922254+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.106","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: ERCC6 as Green List (high evidence)","entity_name":"ERCC6","entity_type":"gene"},{"created":"2021-08-15T12:52:07.909285+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.106","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: ercc6 has been classified as Green List (High Evidence).","entity_name":"ERCC6","entity_type":"gene"},{"created":"2021-08-15T12:51:30.579432+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.105","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: LIG4 as ready","entity_name":"LIG4","entity_type":"gene"},{"created":"2021-08-15T12:51:30.570628+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.105","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: lig4 has been classified as Green List (High Evidence).","entity_name":"LIG4","entity_type":"gene"},{"created":"2021-08-15T12:51:27.872958+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.105","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: LIG4 were changed from microcephaly, growth retardation, immunodeficiency, developmental delay to LIG4 syndrome, MIM# 606593; microcephaly, growth retardation, immunodeficiency, developmental delay","entity_name":"LIG4","entity_type":"gene"},{"created":"2021-08-15T12:51:16.705905+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.104","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: LIG4 were set to 11779494,  16088910,","entity_name":"LIG4","entity_type":"gene"},{"created":"2021-08-15T12:51:03.536880+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.103","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: LIG4 as Green List (high evidence)","entity_name":"LIG4","entity_type":"gene"},{"created":"2021-08-15T12:51:03.525137+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.103","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: lig4 has been classified as Green List (High Evidence).","entity_name":"LIG4","entity_type":"gene"},{"created":"2021-08-15T12:42:57.542164+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.102","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: STAT5B as ready","entity_name":"STAT5B","entity_type":"gene"},{"created":"2021-08-15T12:42:57.531395+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.102","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: stat5b has been classified as Green List (High Evidence).","entity_name":"STAT5B","entity_type":"gene"},{"created":"2021-08-15T12:42:54.457678+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.102","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: STAT5B were changed from  to Growth hormone insensitivity with immune dysregulation 1, autosomal recessive, MIM# 245590; Growth hormone insensitivity with immune dysregulation 2, autosomal dominant, MIM# 618985","entity_name":"STAT5B","entity_type":"gene"},{"created":"2021-08-15T12:42:46.659959+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.101","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: STAT5B were set to ","entity_name":"STAT5B","entity_type":"gene"},{"created":"2021-08-15T12:42:38.398068+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.100","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: STAT5B as Green List (high evidence)","entity_name":"STAT5B","entity_type":"gene"},{"created":"2021-08-15T12:42:38.388875+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.100","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: stat5b has been classified as Green List (High Evidence).","entity_name":"STAT5B","entity_type":"gene"},{"created":"2021-08-15T12:42:30.019549+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.99","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: STAT5B: Rating: GREEN; Mode of pathogenicity: None; Publications: 13679528, 15827093, 16787985, 17389811, 29844444; Phenotypes: Growth hormone insensitivity with immune dysregulation 1, autosomal recessive, MIM# 245590, Growth hormone insensitivity with immune dysregulation 2, autosomal dominant, MIM# 618985; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal","entity_name":"STAT5B","entity_type":"gene"},{"created":"2021-08-15T12:39:02.031013+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.99","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: TBCE as ready","entity_name":"TBCE","entity_type":"gene"},{"created":"2021-08-15T12:39:01.982038+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.99","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: tbce has been classified as Green List (High Evidence).","entity_name":"TBCE","entity_type":"gene"},{"created":"2021-08-15T12:38:59.040442+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.99","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: TBCE were changed from  to Kenny-Caffey syndrome, type 1, MIM# 244460; Hypoparathyroidism-retardation-dysmorphism syndrome, MIM# 241410, Sanjad-Sakati syndrome","entity_name":"TBCE","entity_type":"gene"},{"created":"2021-08-15T12:38:52.310610+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.98","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: TBCE were set to ","entity_name":"TBCE","entity_type":"gene"},{"created":"2021-08-15T12:38:43.644521+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.97","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: TBCE as Green List (high evidence)","entity_name":"TBCE","entity_type":"gene"},{"created":"2021-08-15T12:38:43.631609+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.97","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: tbce has been classified as Green List (High Evidence).","entity_name":"TBCE","entity_type":"gene"},{"created":"2021-08-15T12:38:34.349721+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.96","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: TBCE: Rating: GREEN; Mode of pathogenicity: None; Publications: 12389028, 26029652, 33010201, 30638765; Phenotypes: Kenny-Caffey syndrome, type 1, MIM# 244460, Hypoparathyroidism-retardation-dysmorphism syndrome, MIM# 241410, Sanjad-Sakati syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"TBCE","entity_type":"gene"},{"created":"2021-08-15T12:30:35.458851+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.8825","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: PLXNA2 as ready","entity_name":"PLXNA2","entity_type":"gene"},{"created":"2021-08-15T12:30:35.448360+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.8825","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: plxna2 has been classified as Amber List (Moderate Evidence).","entity_name":"PLXNA2","entity_type":"gene"},{"created":"2021-08-15T12:30:26.493620+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.8825","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: PLXNA2 as Amber List (moderate evidence)","entity_name":"PLXNA2","entity_type":"gene"},{"created":"2021-08-15T12:30:26.483516+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.8825","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: plxna2 has been classified as Amber List (Moderate Evidence).","entity_name":"PLXNA2","entity_type":"gene"},{"created":"2021-08-15T12:30:06.784955+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.8824","user_name":"Zornitza Stark","item_type":"entity","text":"gene: PLXNA2 was added\ngene: PLXNA2 was added to Mendeliome. Sources: Literature\nMode of inheritance for gene: PLXNA2 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: PLXNA2 were set to 34327814\nPhenotypes for gene: PLXNA2 were set to Intellectual disability; Abnormality of the face; Failure to thrive; Abnormal heart morphology\nReview for gene: PLXNA2 was set to AMBER\nAdded comment: Altuame et al (2021 - PMID: 34327814) describe 3 individuals from 2 consanguineous Arab families with biallelic PLXNA2 variants.\r\n\r\nThe index patient from the 1st family presented with CHD (hypoplastic right ventricle, ASD), DD and moderate ID (IQ of 40), failure to thrive as well as some dysmorphic features (obtuse mandibular angle, mild overbite, synophrys with downslanting p-f, strabismus, etc). There were additional features (eg. postaxial polydactyly) which were found in other affected and unaffected family members. \r\n\r\nExome sequencing with autozygome analysis revealed homozygosity for a PLXNA2 stopgain variant (NM_025179:c.3603C>A / p.(Cys1201*)). \r\n\r\nSanger confirmation was carried out and segregation analyses confirmed carrier status of the unaffected parents and a sib as well as a brother homozygous for the same variant. Clinical evaluation of the latter, following this finding revealed borderline intellectual functioning, ADHD, failure to thrive. There was no mandibular anomaly or overbite and no clinical evidence of CHD (no echo performed).\r\n\r\nThe index patient from the 2nd consanguineous family was evaluated for ID (IQ of 63), with previous borderline motor development, ADHD and some dysmorphic features (obtuse mandibular angle and overbite). There was no clinical evidence of CHD (no echo performed).\r\n\r\nExome sequencing with autozygosity mapping revealed a homozygous missense PLXNA2 variant (c.3073G>A / p.(Asp1025Asn), present only once in gnomAD (htz), with rather non-concordant in silico predictions SIFT 0.22, PolyPhen 0.682 and CADD 23.5. The aa was however highly conserved.\r\n\r\nSegregation analysis confirmed carrier state of the parents and 2 unaffected sibs, with a 3rd sib homozygous for the wt allele.\r\n\r\nAs the authors discuss:\r\n*PLXNA2 belongs to the plexin family of genes, encoding transmbembrane proteins functioning as semaphorin receptors. It has predominant expression in neural tissue. The protein is thought to bind semaphorin-3A, -3C or -5 followed by plexin A2 dimerization, activation of its GTPase-activating protein domain, negative regulation of Rap1B GTPase and initiation of a signal transduction cascade mediating axonal repulsion/guidance, dendritic guidance, neuronal migration.\r\n*Murine Plxna2 knockout models display structural brain defects. In addition they display congenital heart defects incl. persistent truncus arteriosus and interrupted aortic arch.\r\n*Rare CNVs in adult humans with tetralogy of Fallot have suggested a potential role of PLXNA2 in cardiac development and CHD.\r\n*Expression and the role of PLXNA2 in human chondrocytes as well as a GWAS in 240 japanese patients with mandibular prognathism where PLXNA2 was suggested as a susceptibility locus.\r\n\r\nOverall, the authors recognize some common features (as for cognitive functioning, some dysmorphic features incl. obtuse mandibular angle and overbite in 2 unrelated subjects, failure to thrive 3/3) and provide plausible explanations for the variability / discordance of others eg:\r\n- Cyanotic heart disease explaining discordance in cognitive outcome among sibs\r\n- Incomplete penetrance for CHD (and/or ID or mandibular anomaly) as for few AR disorders and/or \r\n- Additional pathogenic variants possibly explaining the CHD in the first subject.\r\n\r\nThere is no associated phenotype in OMIM or G2P. SysID includes PLXNA2 among the candidate ID genes. \nSources: Literature","entity_name":"PLXNA2","entity_type":"gene"},{"created":"2021-08-15T12:28:38.808660+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.4055","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: PLXNA2 as ready","entity_name":"PLXNA2","entity_type":"gene"},{"created":"2021-08-15T12:28:38.799522+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.4055","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: plxna2 has been classified as Amber List (Moderate Evidence).","entity_name":"PLXNA2","entity_type":"gene"},{"created":"2021-08-15T12:28:33.606644+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.4055","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: PLXNA2 as Amber List (moderate evidence)","entity_name":"PLXNA2","entity_type":"gene"},{"created":"2021-08-15T12:28:33.595118+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.4055","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: plxna2 has been classified as Amber List (Moderate Evidence).","entity_name":"PLXNA2","entity_type":"gene"},{"created":"2021-08-15T12:25:23.460654+10:00","panel_name":"Congenital Diarrhoea","panel_id":89,"panel_version":"1.7","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: SLC51A as ready","entity_name":"SLC51A","entity_type":"gene"},{"created":"2021-08-15T12:25:23.449744+10:00","panel_name":"Congenital Diarrhoea","panel_id":89,"panel_version":"1.7","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: slc51a has been classified as Red List (Low Evidence).","entity_name":"SLC51A","entity_type":"gene"},{"created":"2021-08-15T12:25:15.778032+10:00","panel_name":"Congenital Diarrhoea","panel_id":89,"panel_version":"1.7","user_name":"Zornitza Stark","item_type":"entity","text":"gene: SLC51A was added\ngene: SLC51A was added to Congenital Diarrhoea. Sources: Literature\nMode of inheritance for gene: SLC51A was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: SLC51A were set to 31863603\nPhenotypes for gene: SLC51A were set to Cholestasis, progressive familial intrahepatic, 6, MIM# 619484\nReview for gene: SLC51A was set to RED\nAdded comment: Single individual reported with homozygous LoF variant, who presented with chronic malabsorptive diarrhoea, easy bruising, episodes of prolonged bleeding that required blood transfusions, and failure to thrive. Laboratory testing at age 2.5 years showed elevated liver transaminases and alkaline phosphatase. Liver biopsy demonstrated portal and periportal fibrosis and hepatocytes with foci of hepatocytic cholestasis. Analysis of bile acids in a blood spot were normal. Treatment with ursodiol and cholestyramine was started at 5 years of age. The coagulopathy resolved and his growth was adequate, but his liver transaminases, direct bilirubin, and GGT levels remained elevated. \nSources: Literature","entity_name":"SLC51A","entity_type":"gene"},{"created":"2021-08-15T12:23:48.721811+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.8823","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: SLC51A as ready","entity_name":"SLC51A","entity_type":"gene"},{"created":"2021-08-15T12:23:48.712798+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.8823","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: slc51a has been classified as Red List (Low Evidence).","entity_name":"SLC51A","entity_type":"gene"},{"created":"2021-08-15T12:23:39.807834+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.8823","user_name":"Zornitza Stark","item_type":"entity","text":"gene: SLC51A was added\ngene: SLC51A was added to Mendeliome. Sources: Literature\nMode of inheritance for gene: SLC51A was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: SLC51A were set to 31863603\nPhenotypes for gene: SLC51A were set to Cholestasis, progressive familial intrahepatic, 6, MIM# 619484\nReview for gene: SLC51A was set to RED\nAdded comment: Single individual reported with homozygous LoF variant, who presented with chronic malabsorptive diarrhoea, easy bruising, episodes of prolonged bleeding that required blood transfusions, and failure to thrive. Laboratory testing at age 2.5 years showed elevated liver transaminases and alkaline phosphatase. Liver biopsy demonstrated portal and periportal fibrosis and hepatocytes with foci of hepatocytic cholestasis. Analysis of bile acids in a blood spot were normal. Treatment with ursodiol and cholestyramine was started at 5 years of age. The coagulopathy resolved and his growth was adequate, but his liver transaminases, direct bilirubin, and GGT levels remained elevated. \nSources: Literature","entity_name":"SLC51A","entity_type":"gene"},{"created":"2021-08-15T12:23:02.948975+10:00","panel_name":"Cholestasis","panel_id":78,"panel_version":"0.203","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: SLC51A as ready","entity_name":"SLC51A","entity_type":"gene"},{"created":"2021-08-15T12:23:02.936004+10:00","panel_name":"Cholestasis","panel_id":78,"panel_version":"0.203","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: slc51a has been classified as Red List (Low Evidence).","entity_name":"SLC51A","entity_type":"gene"},{"created":"2021-08-15T12:22:13.083501+10:00","panel_name":"Cholestasis","panel_id":78,"panel_version":"0.203","user_name":"Zornitza Stark","item_type":"entity","text":"gene: SLC51A was added\ngene: SLC51A was added to Cholestasis. Sources: Literature\nMode of inheritance for gene: SLC51A was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: SLC51A were set to 31863603\nPhenotypes for gene: SLC51A were set to Cholestasis, progressive familial intrahepatic, 6, MIM#\t619484\nReview for gene: SLC51A was set to RED\nAdded comment: Single individual reported with homozygous LoF variant, who presented with chronic malabsorptive diarrhoea, easy bruising, episodes of prolonged bleeding that required blood transfusions, and failure to thrive. Laboratory testing at age 2.5 years showed elevated liver transaminases and alkaline phosphatase. Liver biopsy demonstrated portal and periportal fibrosis and hepatocytes with foci of hepatocytic cholestasis. Analysis of bile acids in a blood spot were normal. Treatment with ursodiol and cholestyramine was started at 5 years of age. The coagulopathy resolved and his growth was adequate, but his liver transaminases, direct bilirubin, and GGT levels remained elevated. \nSources: Literature","entity_name":"SLC51A","entity_type":"gene"},{"created":"2021-08-15T12:18:40.735885+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.4054","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: SUPT16H were changed from Intellectual disability; Abnormality of the corpus callosum to Neurodevelopmental disorder with dysmorphic facies and thin corpus callosum, MIM# 619480; Intellectual disability; Abnormality of the corpus callosum","entity_name":"SUPT16H","entity_type":"gene"},{"created":"2021-08-15T12:18:12.303331+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.4053","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: SUPT16H: Changed phenotypes: Neurodevelopmental disorder with dysmorphic facies and thin corpus callosum, MIM# 619480, Intellectual disability, Abnormality of the corpus callosum","entity_name":"SUPT16H","entity_type":"gene"},{"created":"2021-08-15T12:17:57.769655+10:00","panel_name":"Callosome","panel_id":205,"panel_version":"0.310","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: SUPT16H were changed from Intellectual disability; Abnormality of the corpus callosum to Neurodevelopmental disorder with dysmorphic facies and thin corpus callosum, MIM# 619480; Intellectual disability; Abnormality of the corpus callosum","entity_name":"SUPT16H","entity_type":"gene"},{"created":"2021-08-15T12:17:22.732203+10:00","panel_name":"Callosome","panel_id":205,"panel_version":"0.309","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: SUPT16H: Changed phenotypes: Neurodevelopmental disorder with dysmorphic facies and thin corpus callosum, MIM# 619480, Intellectual disability, Abnormality of the corpus callosum","entity_name":"SUPT16H","entity_type":"gene"},{"created":"2021-08-15T12:17:06.515575+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.8822","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: SUPT16H were changed from Intellectual disability; Abnormality of the corpus callosum to Neurodevelopmental disorder with dysmorphic facies and thin corpus callosum, MIM# 619480; Intellectual disability; Abnormality of the corpus callosum","entity_name":"SUPT16H","entity_type":"gene"},{"created":"2021-08-15T12:16:44.099884+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"0.8821","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: SUPT16H: Changed phenotypes: Neurodevelopmental disorder with dysmorphic facies and thin corpus callosum, MIM# 619480, Intellectual disability, Abnormality of the corpus callosum","entity_name":"SUPT16H","entity_type":"gene"},{"created":"2021-08-15T11:25:29.386370+10:00","panel_name":"Early-onset Parkinson disease","panel_id":26,"panel_version":"0.110","user_name":"Bryony Thompson","item_type":"entity","text":"Phenotypes for gene: FMR1 were changed from  to Fragile X tremor/ataxia syndrome MIM#300623; Fragile X syndrome MIM#300624","entity_name":"FMR1","entity_type":"gene"},{"created":"2021-08-15T11:24:23.973371+10:00","panel_name":"Early-onset Parkinson disease","panel_id":26,"panel_version":"0.109","user_name":"Bryony Thompson","item_type":"entity","text":"Publications for gene: FMR1 were set to ","entity_name":"FMR1","entity_type":"gene"},{"created":"2021-08-15T11:23:52.211958+10:00","panel_name":"Early-onset Parkinson disease","panel_id":26,"panel_version":"0.108","user_name":"Bryony Thompson","item_type":"entity","text":"Mode of inheritance for gene: FMR1 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)","entity_name":"FMR1","entity_type":"gene"},{"created":"2021-08-15T02:53:36.920595+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"0.4053","user_name":"Konstantinos Varvagiannis","item_type":"entity","text":"gene: PLXNA2 was added\ngene: PLXNA2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature,Other\nMode of inheritance for gene: PLXNA2 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: PLXNA2 were set to 34327814\nPhenotypes for gene: PLXNA2 were set to Intellectual disability; Abnormality of the face; Failure to thrive; Abnormal heart morphology\nPenetrance for gene: PLXNA2 were set to Incomplete\nReview for gene: PLXNA2 was set to AMBER\nAdded comment: Altuame et al (2021 - PMID: 34327814) describe 3 individuals from 2 consanguineous Arab families with biallelic PLXNA2 variants.\r\n\r\nThe index patient from the 1st family presented with CHD (hypoplastic right ventricle, ASD),  DD and moderate ID (IQ of 40), failure to thrive as well as some dysmorphic features (obtuse mandibular angle, mild overbite, synophrys with downslanting p-f, strabismus, etc). There were additional features (eg. postaxial polydactyly) which were found in other affected and unaffected family members. \r\n\r\nExome sequencing with autozygome analysis revealed homozygosity for a PLXNA2 stopgain variant (NM_025179:c.3603C>A / p.(Cys1201*)).  \r\n\r\nSanger confirmation was carried out and segregation analyses confirmed carrier status of the unaffected parents and a sib as well as a brother homozygous for the same variant. Clinical evaluation of the latter, following this finding revealed borderline intellectual functioning, ADHD, failure to thrive. There was no mandibular anomaly or overbite and no clinical evidence of CHD (no echo performed).\r\n\r\nThe index patient from the 2nd consanguineous family was evaluated for ID (IQ of 63), with previous borderline  motor development, ADHD and some dysmorphic features (obtuse mandibular angle and overbite). There was no clinical evidence of CHD (no echo performed).\r\n\r\nExome sequencing with autozygosity mapping revealed a homozygous missense PLXNA2 variant (c.3073G>A / p.(Asp1025Asn), present only once in gnomAD (htz), with rather non-concordant in silico predictions SIFT 0.22, PolyPhen 0.682 and CADD 23.5. The aa was however highly conserved.\r\n\r\nSegregation analysis confirmed carrier state of the parents and 2 unaffected sibs, with a 3rd sib homozygous for the wt allele.\r\n\r\nAs the authors discuss:\r\n*PLXNA2 belongs to the plexin family of genes, encoding transmbembrane proteins functioning as semaphorin receptors. It has predominant expression in neural tissue. The protein is thought to bind semaphorin-3A, -3C or -5 followed by plexin A2 dimerization, activation of its GTPase-activating protein domain, negative regulation of Rap1B GTPase and initiation of a signal transduction cascade mediating axonal repulsion/guidance, dendritic guidance, neuronal migration.\r\n*Murine Plxna2 knockout models display structural brain defects. In addition they display congenital heart defects incl. persistent truncus arteriosus and interrupted aortic arch.\r\n*Rare CNVs in adult humans with tetralogy of Fallot have suggested a potential role of PLXNA2 in cardiac development and CHD.\r\n*Expression and the role of PLXNA2 in human chondrocytes as well as a GWAS in 240 japanese patients with mandibular prognathism where PLXNA2 was suggested as a susceptibility locus.\r\n\r\nOverall, the authors recognize some common features (as for cognitive functioning, some dysmorphic features incl. obtuse mandibular angle and overbite in 2 unrelated subjects, failure to thrive 3/3) and provide plausible explanations for the variability / discordance of others eg:\r\n- Cyanotic heart disease  explaining discordance in cognitive outcome among sibs\r\n- Incomplete penetrance for CHD (and/or ID or mandibular anomaly) as for few AR disorders and/or \r\n- Additional pathogenic variants possibly explaining the CHD in the first subject.\r\n\r\nThere is no associated phenotype in OMIM or G2P. SysID includes PLXNA2 among the candidate ID genes. \nSources: Literature, Other","entity_name":"PLXNA2","entity_type":"gene"},{"created":"2021-08-14T19:01:34.516740+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.96","user_name":"Zornitza Stark","item_type":"panel","text":"removed gene:THRB from the panel","entity_name":null,"entity_type":null},{"created":"2021-08-14T15:28:12.715053+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.95","user_name":"Zornitza Stark","item_type":"panel","text":"removed gene:IGFBP3 from the panel","entity_name":null,"entity_type":null},{"created":"2021-08-14T15:27:53.842449+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.94","user_name":"Zornitza Stark","item_type":"panel","text":"removed gene:IGFBP1 from the panel","entity_name":null,"entity_type":null},{"created":"2021-08-14T15:23:53.099483+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.93","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: MRAS as ready","entity_name":"MRAS","entity_type":"gene"},{"created":"2021-08-14T15:23:53.089992+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.93","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: mras has been classified as Green List (High Evidence).","entity_name":"MRAS","entity_type":"gene"},{"created":"2021-08-14T15:23:42.621647+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.93","user_name":"Zornitza Stark","item_type":"entity","text":"Mode of pathogenicity for gene: MRAS was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments","entity_name":"MRAS","entity_type":"gene"},{"created":"2021-08-14T15:23:36.038265+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.92","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: MRAS as Green List (high evidence)","entity_name":"MRAS","entity_type":"gene"},{"created":"2021-08-14T15:23:36.029096+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.92","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: mras has been classified as Green List (High Evidence).","entity_name":"MRAS","entity_type":"gene"},{"created":"2021-08-14T15:23:26.909011+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.91","user_name":"Zornitza Stark","item_type":"entity","text":"gene: MRAS was added\ngene: MRAS was added to Growth failure in early childhood. Sources: Expert Review\nMode of inheritance for gene: MRAS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: MRAS were set to 28289718; 31173466; 31108500; 31173466\nPhenotypes for gene: MRAS were set to Noonan syndrome 11, MIM#618499\nReview for gene: MRAS was set to GREEN\nAdded comment: At least 6 unrelated individuals reported. \nSources: Expert Review","entity_name":"MRAS","entity_type":"gene"},{"created":"2021-08-14T15:19:28.053245+10:00","panel_name":"Pituitary hormone deficiency","panel_id":3236,"panel_version":"0.13","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: BTK as ready","entity_name":"BTK","entity_type":"gene"},{"created":"2021-08-14T15:19:28.043416+10:00","panel_name":"Pituitary hormone deficiency","panel_id":3236,"panel_version":"0.13","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: btk has been classified as Green List (High Evidence).","entity_name":"BTK","entity_type":"gene"},{"created":"2021-08-14T15:19:12.438803+10:00","panel_name":"Pituitary hormone deficiency","panel_id":3236,"panel_version":"0.13","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: BTK: Rating: GREEN; Mode of pathogenicity: None; Publications: 8013627, 7849697, 9554752; Phenotypes: Isolated growth hormone deficiency, type III, with agammaglobulinaemia, MIM# 307200; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females","entity_name":"BTK","entity_type":"gene"},{"created":"2021-08-14T15:18:08.048082+10:00","panel_name":"Growth failure in early childhood","panel_id":3631,"panel_version":"0.90","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: BTK were set to 8013627; 7849697","entity_name":"BTK","entity_type":"gene"}]}