Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: LAMTOR2Comment on list classification: Gene was reassessed following a recent Amber review by Zornitza Stark. Although there has only been one family reported to date, the rating was based on multiple Green GMS expert reviews as the functional support was deemed sufficiently compelling. Therefore, the Green gene rating will be maintained on this panel.Created: 10 Aug 2021, 3:04 p.m. | Last Modified: 10 Aug 2021, 3:04 p.m.
Panel Version: 2.455
Single family reported with some supportive functional data. We have downgraded to Amber on our panel.Created: 28 Jul 2021, 3:45 a.m. | Last Modified: 28 Jul 2021, 3:45 a.m.
Panel Version: 2.452
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Immunodeficiency due to defect in MAPBP-interacting protein, MIM# 610798
Publications
agree with green geneCreated: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
YES- this is covered on our targeted exomeCreated: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
neutropenia
Publications
Gene rating submitted by Kimberly Gilmour and Austen Worth on behalf of London North GLH for the GMS Immunology specialist test group. As discussed with the GMS Immunology Specialist Test Group during webex call 28th March 2019 and confirmed in follow up email 6th September the Specialist Test Group all agreed there is enough evidence to rate this gene Green.Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
Gene rating submitted by Tracy Briggs, David Gokhale and Abigal Rousseau on behalf of North West GLH for the GMS Immunology specialist test group. As discussed with the GMS Immunology Specialist Test Group during webex call 28th March 2019 and confirmed in follow up email on 20th June the Specialist Test Group all agreed there is enough evidence to rate this gene Green.Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
Although there is only one large family reported in the literature, the functional evidence is thought to be compelling enough to rate this gene GreenCreated: 2 Jul 2018, 1:35 p.m.
OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): LAMTOR2 .PanelApp HGNC gene symbol check: LAMTOR2 . IUIS Disease: P14/LAMTOR2 deficiency . IUIS Inheritance: AR .T cells: Low thymic output, normal in vitro proliferation, .B cells: N/A, .IUIS Other affected cells: N + M. IUIS Associated features: Neutropenia, Hypogammaglobulinemia CD8 cytotoxicity, partial albinism, growth failure . IUIS Major category: Congenital defects of phagocyte number or function. IUIS Subcategory: Congenital NeutropeniasCreated: 2 Jul 2018, 10:35 a.m.
Comment on list classification: Only one pathogenic variant reported in one family. In view of expert review Green, presence on Victorian Clinical Genetics Services panel (2 unrelated cases criteria) and functional info this gene from mouse model this gene was made Green.Created: 27 Jun 2018, 10:50 a.m.
Comment on publications: added publications on mouse model
Mutated, dysfunctional p14 leads to a human immunodeficiency disorder with endosomal/lysosomal defects in immune cells. Because p14 participates in the regulation of endosomal trafficking, growth factor signaling, and cell proliferation, we investigated the role of p14 in mouse DCs/LCs using a conditional knockout mouse model..p14-mediated disruption of the LAMTOR complex which results in the malfunction of both ERK and mTOR signal pathways. Hence, we conclude that p14 acts as a novel and essential regulator of LC homeostasis in vivo.Created: 27 Jun 2018, 10:48 a.m.
Comment on publications: To date, it has been described in four members of one Caucasian family, Bohn et al. (2007) PMID: 17195838Created: 27 Jun 2018, 10:20 a.m.
This gene was absent from the original PanelApp PID panel dataset (review April 2018). However it was listed in external expert immunodeficiency diagnostic gene list(s) GOSH or GRID. In this combined PID panel, this gene has been rated as AMBER and needs further curational review to assess pertinence prior to v1.Created: 20 Apr 2018, 12:25 p.m.
Original metadata downloaded from ESID Registry. ESID_Gene_original: P14, PanelApp HGNC gene symbol check: LAMTOR2, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Phagocytic disorders / Congenital neutropenia / Congenital neutropeniaCreated: 17 Apr 2018, 12:29 p.m.
Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: LAMTOR2, GRID_Gene_Symbol: LAMTOR2, GRID_Transcript_ENS_Community submitted: ENST00000368305, GRID_Transcript_RefSeq: NM_014017.3, GRID_Transcript_ENS_used_on_Production: ENST00000368305Created: 17 Apr 2018, 12:12 p.m.
Gene: lamtor2 has been classified as Green List (High Evidence).
Source NHS GMS was added to LAMTOR2.
Source North West GLH was added to LAMTOR2.
Source London North GLH was added to LAMTOR2.
2018-07-12 Louise Daugherty (Genomics England Curator) promoted panel to v1.0. Reviews were assessed, and panel was revised according to expert reviews and further in-house curation based on PanelApp guidelines. Previous panels (A- or hypo-gammaglobulinaemia, Congenital neutropaenia, Agranulocytosis, Combined B and T cell defect, Inherited complement deficiency and SCID panels) that were merged with this panel, were checked again for any changes/new reviews prior to versioning of this panel, these merged panels are now retired/made internal.
Gene: lamtor2 has been classified as Green List (High Evidence).
Phenotypes for gene LAMTOR2 were set to Immunodeficiency due to defect in MAPBP-interacting protein, 610798, Congenital neutropenia, Primary immunodeficiency syndrome due to p14 deficiency, Neutropenia, Hypogammaglobulinemia CD8 cytotoxicity, partial albinism, growth failure, Congenital defects of phagocyte number or function
Gene: lamtor2 has been classified as Green List (High Evidence).
Gene: lamtor2 has been classified as Green List (High Evidence).
Publications for gene: LAMTOR2 were set to 17195838; 24092934; 22427693; 28593997
Publications for gene: LAMTOR2 were set to 17195838; 24092934; 22427693
Publications for gene: LAMTOR2 were set to 17195838
Phenotypes for gene: LAMTOR2 were set to Immunodeficiency due to defect in MAPBP-interacting protein, 610798; Congenital neutropenia; Primary immunodeficiency syndrome due to p14 deficiency
IUIS Classification February 2018 was added to LAMTOR2. Panel: Primary immunodeficiency disorders
Victorian Clinical Genetics Services was added to LAMTOR2. Panel: Primary immunodeficiency disorders
Expert Review Amber was added to LAMTOR2. Panel: Primary immunodeficiency disorders
ESID Registry 20171117 was added to LAMTOR2. Panel: Primary immunodeficiency disorders Phenotypes for gene LAMTOR2 were set to Immunodeficiency due to defect in MAPBP-interacting protein, Congenital neutropenia
Phenotypes for gene LAMTOR2 were set to Immunodeficiency due to defect in MAPBP-interacting protein
LAMTOR2 was added to Primary immunodeficiency disorders panel. Sources: GRID V2.0
LAMTOR2 was created by Louise Daugherty