Intellectual disability - microarray and sequencing
Gene: FGFR2Comment on list classification: Changed rating of gene from Red to Amber. This gene was rated as Amber in v2.467 and incorrectly automatically demoted to Red 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, 9:31 p.m.
Comment when marking as ready: Causation is clear for the craniosynostosis related syndromes listed. Although ID is a reported feature these conditions, they would be expected to present in a syndromic manner with craniosynostosis prior to ID. This, along with the fact that there are a handful of recurrent missense variants, means that the utility of calling all variants in this gene in a cohort that includes non-syndromic ID is unlikely to be of benefit.Created: 21 Dec 2017, 10:22 a.m.
Comment on list classification: Causation is clear for the craniosynostosis related syndromes listed. Although ID is a reported feature these conditions, they would be expected to present in a syndromic manner with craniosynostosis prior to ID. This, along with the fact that there are a handful of recurrent missense variants, means that the utility of calling all variants in this gene in a cohort that includes non-syndromic ID is unlikely to be of benefit.Created: 21 Dec 2017, 10:22 a.m.
This is a confirmed DD gene for Antley-Bixler syndrome, Apert syndrome and Crouzon syndrome which include ID as a HPO term. It is a confirmed DD gene for Beare-Stevenson Cutis Gyrata syndrome, which includes global developmental delay as a HPO term. Activating mutations.Created: 13 Dec 2017, 9:46 p.m.
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Antley-Bixler syndrome; Apert syndrome; Crouzon syndrome; Beare-Stevenson Cutis Gyrata syndrome
Publications
Mode of pathogenicity
Other
Phenotypes
CROUZON SYNDROME (CS)
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_gilissen_2014_known;in_UKGTN_v12 . Main mutation mechanism : Activating; UncertainCreated: 27 Jul 2017, 5:49 p.m.
Evidences key, gene present in following gene lists and main mutation mechanism : ddg2p_20141118; ddg2p_20141118_conf; ddg2p_201507; ddg2p_201507_conf; gilissen_2014_known; UKGTN_v12; Nijmegen_ID_diagnostic; Nijmegen_ID_candidates; GEL_ID_red_20160217; neuro_20160418_strict; Activating; Uncertain. 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, 12:27 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications
Mode of pathogenicity
Other
Mode of inheritance for gene: FGFR2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Tag Q1_22_MOI was removed from gene: FGFR2.
Tag Q1_22_MOI tag was added to gene: FGFR2.
Gene: fgfr2 has been classified as Amber List (Moderate Evidence).
Source Victorian Clinical Genetics Services was added to FGFR2.
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.
Model of inheritance for gene FGFR2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene FGFR2 was set to ['16061565']
The Gel status was updated for this whole panel
The Gel status was updated for this whole panel
FGFR2 was added to Intellectual disabilitypanel. Source: Expert Review Red
FGFR2 was added to Intellectual disabilitypanel. Sources: Radboud University Medical Center, Nijmegen