Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: LAMTOR2

Comment 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

I don't know

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

• 17195838
• 24092934

Green List (high evidence)

agree with green gene

Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.

Panel Version: 1.94

Green List (high evidence)

YES- this is covered on our targeted exome

Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.

Panel Version: 1.94

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
neutropenia

Publications

• 17195838

Green List (high evidence)

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 Green

Created: 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 Neutropenias

Created: 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: 17195838

Created: 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 neutropenia

Created: 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: ENST00000368305

Created: 17 Apr 2018, 12:12 p.m.