Intellectual disability - microarray and sequencing
Gene: GBA2Following discussion with the clinical team, this gene has been demoted from Amber to Red, in accordance with the external review by Zornitza StarkCreated: 17 Aug 2020, 10:01 a.m. | Last Modified: 17 Aug 2020, 10:01 a.m.
Panel Version: 3.252
Progressive neurodegenerative condition with childhood onset rather than truly ID.Created: 4 Feb 2020, 9:28 a.m. | Last Modified: 4 Feb 2020, 9:28 a.m.
Panel Version: 3.0
Phenotypes
Spastic paraplegia 46, autosomal recessive, MIM#614409
Comment on phenotypes: added phenotype from Sarah Leigh (Genomics England), 5 Mar 2018 reviewCreated: 14 Mar 2018, 11:52 a.m.
Comment on publications: Added publications from Sarah Leigh (Genomics England), 5 Mar 2018 reviewCreated: 14 Mar 2018, 11:51 a.m.
Comment when marking as ready: Phenotype not a clear fit for this panel on the current evidence.Created: 6 Mar 2018, 4:52 p.m.
Comment on list classification: I recognise that there are cases with intellectual impairment reported, however all cases reported to date have initially presented with gait disturbance or spasticity in the 1st-2nd decades. Therefore on the current evidence, the best place to capture phenotypes associated with this gene would be the HSP panel. If evidence emerges of a primary ID phenotype (rather than more complex neurological decline) then this can be re-considered.Created: 6 Mar 2018, 4:51 p.m.
Comment on list classification: I recognise that there are cases with intellectual impairment reported, however all cases reported to date have initially presented with gait disturbance or spasticity in the 1st-2nd decades. Therefore on the current evidence, the best place to capture phenotypes associated with this gene would be the HSP panel. If evidence emerges of a primary ID phenotype (rather than more complex neurological decline) then this can be re-considered.Created: 6 Mar 2018, 4:51 p.m.
Comment on phenotypes: Mild to moderate mental retardation reported in some patients and overall cognitive decline generally reported according PMID 23332916Created: 5 Mar 2018, 11:43 a.m.
Comment when marking as ready: Spastic paraplegia 46, autosomal recessive 614409Created: 5 Mar 2018, 11:40 a.m.
Associated with phenotype in OMIM and as a confirmed G2P association for Spastic paraplegia 46, autosomal recessive 614409, however, intellectual disability is not a common feature of this phenotype.
Based on report of a variant in two unrelated cases of Marinesco-Sjögren-Like Syndrome (PMID 28052128) in addition to at least three cases of Spastic paraplegia 46, autosomal recessive 614409 that display intellectual disability (PMIDs 23332916;23332917;24252062)Created: 5 Mar 2018, 11:17 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
AUTOSOMAL-RECESSIVE CEREBELLAR ATAXIA WITH SPASTICITY.
Publications
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_omim_20150205_movement;in_movement_disorder_list . Main mutation mechanism : Loss of functionCreated: 27 Jul 2017, 6:10 p.m.
Evidences key, gene present in following gene lists and main mutation mechanism : ddg2p_20141118; ddg2p_20141118_conf; ddg2p_201507; ddg2p_201507_conf; omim_20150205_movement; manju_list; GEL_ID_red_20160217; neuro_20160418_strict; Loss of function. 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, 12:31 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Publications
Comment on list classification: Not an ID geneCreated: 7 Feb 2016, 8:47 p.m.
Source: Expert Review Red was removed from gene: GBA2
Publications for GBA2 were set to 23332916; 23332917; 24252062; 28052128
Phenotypes for GBA2 were set to Spastic paraplegia 46, autosomal recessive, 614409
Publications for GBA2 were set to 23332917; 23332916; 23332917; 24252062; 28052128
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.
Expert Review Amber was added to GBA2. Panel: Intellectual disability
This gene has been classified as Red List (Low Evidence).
This gene has been classified as Red List (Low Evidence).
The Gel status was updated for this whole panel
The Gel status was updated for this whole panel
GBA2 was created by ellenmcdonagh
GBA2 was added to Intellectual disabilitypanel. Sources: Expert Review Amber