Intellectual disability - microarray and sequencing
Gene: PIK3CAComment on mode of inheritance: Changed MOI from 'Unknown' in order to capture appropriate variants within this gene in our current tiering pipeline.Created: 1 Nov 2018, 3:33 p.m.
Comment on mode of inheritance: Somatic (post-zygotic) variants in this gene can cause Megalencephaly-capillary malformation-polymicrogyria syndrome, a feature of which is variable ID.Created: 4 Jan 2018, 11:06 a.m.
Comment on phenotypes: Gene2Phenotype confirmed gene with ID related disease – Megalencephaly-capillary malformation-polymicrogyria syndrome, somatic 3Created: 4 Jan 2018, 10:55 a.m.
Comment when marking as ready: Somatic (post-zygotic) variants in this gene can cause Megalencephaly-capillary malformation-polymicrogyria syndrome, a feature of which is variable ID. The phenotype is appropriate for inclusion, however the reliability of pick-up is questionable given the somatic mosaic nature. Green rating in line with other related panels (e.g. Regional overgrowth disorders).Created: 21 Dec 2017, 1:39 p.m.
This is a pertinent gene from the NIHR BioResource - Rare Diseases Study (NIHRBR-RD) BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene is on the SPEED_NEURO_20170705 gene list. Evidences used for SPEED NEURO gene list: in_ddg2p_20141118_conf;in_ddg2p_20141118_conf;in_ddg2p_201507;in_ddg2p_201507_conf;in_ddg2p_2_4_2017;in_ddg2p_2_4_2017_conf;in_UKGTN_v12 . Main mutation mechanism : ActivatingCreated: 27 Jul 2017, 8:01 p.m.
Evidences key, gene present in following gene lists and main mutation mechanism : ddg2p_20141118; ddg2p_20141118_conf; ddg2p_201507; ddg2p_201507_conf; UKGTN_v12; Nijmegen_ID_candidates; neuro_20160418_strict; Activating. This is a pertinent gene from the BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene comes from the SPEED_NEURO_v3.0_20170404 gene list. The following experts from the BRIDGE consortium NIHRBR-RD contributed to this panel: - Professor F. Lucy Raymond, Cambridge Institute for Medical Research, University of Cambridge - Manju Kurian, Paediatric neurologist, Great Ormond Street Hosptial - Keren Carss, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Alba Sanchis-Juan, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Marie Erwood NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Louise Daugherty, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation TrustCreated: 19 Jul 2017, 1:06 p.m.
Mode of inheritance
Unknown
Publications
Mode of pathogenicity
Other
Comment on list classification: Changed rating of gene from Amber to Green. This gene was rated as Green in v2.467 and incorrectly automatically demoted to Amber in v2.468. This was due to a defect in the automatic PanelApp uploading tool where a reference gene list was added as a new Source (Victorian Clinical Genetics Services), and under certain conditions associated to previous sources listed, resulted in the rating of the gene being automatically changed when it should not have been.Created: 29 Sep 2018, 7:14 p.m.
Approximately 170 patients have been reported in the literature without significant sex predominance (ORPHA:6004)Created: 12 Jan 2018, 11:34 a.m.
Comment on phenotypes: added OMIM phenotypeCreated: 12 Jan 2018, 11:29 a.m.
Comment on phenotypes: removed : Ovarian cancer, somatic, 167000; Breast cancer, somatic, 114480; Colorectal cancer, somatic, 114500; Gastric cancer, somatic, 613659; Hepatocellular carcinoma, somatic, 114550; Nonsmall cell lung cancer, somatic, 211980; Keratosis, seborrheic, somatic, 182000; Nevus, epidermal, somatic, 162900; CLOVE syndrome, somatic, 612918;Created: 21 Dec 2017, 4:47 p.m.
added somatic and mosaicism tagCreated: 21 Dec 2017, 4:46 p.m.
Comment on list classification: This gene is from an expert list and needs further assessment by the Genomics England curation team to assess inclusion and pertinence to this panel.Created: 20 Jul 2017, 1:16 p.m.
Mode of inheritance for gene: PIK3CA was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Gene: pik3ca has been classified as Green List (High Evidence).
Source Victorian Clinical Genetics Services was added to PIK3CA.
12.03.2018: Due to major updates completed (Phase 1, 2 and 3), this panel was promoted to Version 2 in order to reflect the major updates since November 2017 which have resulted in reviews for 836 genes added by Genomics England Curators and the Clinical Team, 130 new Green genes added to the interpretation pipeline (from 751 to 881 Green genes), and the gene total has increased from 1879 to 1927.
Phenotypes for PIK3CA were set to Megalencephaly-capillary malformation-polymicrogyria syndrome, somatic, 602501; Megalencephaly-capillary malformation-polymicrogyria syndrome, Orphanet:60040
Expert Review Green was added to PIK3CA. Panel: Intellectual disability Model of inheritance for gene PIK3CA was set to Unknown
Phenotypes for PIK3CA were set to Megalencephaly-capillary malformation-polymicrogyria syndrome, somatic, 602501
This gene has been classified as Amber List (Moderate Evidence).
PIK3CA was created by BRIDGE
PIK3CA was added to Intellectual disabilitypanel. Sources: BRIDGE study SPEED NEURO Tier1 Gene