Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: SH2D1A

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)

Comment on list classification: Changed rating of gene from Red to Green. This gene was rated as Green in v2.208 and incorrectly automatically demoted to Red in v2.209. This was due to a defect in the automatic PanelApp uploading tool when a set of publications was added to the panel with the source ‘Other’, 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: 14 Oct 2020, 4:23 p.m. | Last Modified: 14 Oct 2020, 4:23 p.m.

Panel Version: 2.309

The following PubMed IDs were added to entity SH2D1A: 31754776;21119115;25085526. These publications have been associated with OMIM phenotype MIM#308240, which is listed for this entity, by the immunedysregulation subgroup of the Human Phenotype Ontology Immune Mediated Disorders Consortium (https://hpo-immune-mediated-disorders.groups.io/g/update) in August 2020.

Created: 13 Oct 2020, 9:36 a.m. | Last Modified: 13 Oct 2020, 9:36 a.m.

Panel Version: 2.208

Comment on list classification: SH2D1A is associated with Lymphoproliferative syndrome, X-linked, 1 308240 in OMIM. Evidence is from several publications including: Coffey et al. (1998) (PubMed: 9771704) who report mutations in the SH2D1A gene 9 unrelated patients with X-linked lymphoproliferative syndrome, Sumegi et al. (1999) (PubMed: 10556288) report 15 mutations in the SH2D1A gene in those with X-linked lymphoproliferative (Duncan) disease, Brandau et al. (1999) (PubMed: 10556288) report five SH2D1A mutations in patients from five unrelated XLP families. No mutations were found in another three XLP families. Yin et al (1999) (PubMed: 10598819) by report findings of 13 mutations in the SH2D1A gene in 19 typical and 8 atypical XLP patients (by PCR, RT-PCR, and sequence analysis). Other publications such as Lappalainen et al. (2000) (PubMed: 10694488) and Sumegi et al. (2000) (PubMed: 11049992) also report SH2D1A mutations in patients with XLP. Panchal et al (2018) (PubMed: 29670631) gives a more recent review. Sayos et al (1998) (PubMed: 9774102) provided evidence that SH2D1A (SAP) binds to the cytoplasmic tail of a T cell costimulatory protein, signaling lymphocyte activation molecule (SLAM). SH2D1A is also linked to X-linked lymphoproliferative disease in Orphanet.

Created: 1 May 2018, 10:28 a.m.

Added morbid ID from OMIM to phenotypes. Added Duncan disease as a phenotype term

Created: 1 May 2018, 9:37 a.m.

Publications

• 31754776
• 21119115
• 25085526

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

OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): SH2D1A .PanelApp HGNC gene symbol check: SH2D1A . IUIS Disease: SH2D1A deficiency (XLP1) . IUIS Inheritance: XL .T cells: Low, low terminal differentiated effector memory (TEMRA) cells, low nave T cells, poor proliferation, .B cells: Reduced Memory B cells, .IUIS Other affected cells: N/A. IUIS Associated features: EBV, HLH, Lymphoproliferation, Aplastic anaemia, Lymphoma. Hypogammaglobulinemia, Absent iNKT cells. IUIS Major category: Diseases of Immune Dysregulation. IUIS Subcategory: Susceptibility to EBV and Lymphoproliferative Conditions

Created: 2 Jul 2018, 10:35 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: 19 Apr 2018, 3:18 p.m.

Original metadata downloaded from ESID Registry. ESID_Gene_original: SH2D1A (XLP1), PanelApp HGNC gene symbol check: SH2D1A, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Diseases of immune dysregulation / Hemophagocytic Lymphohistiocytosis (HLH) / X-linked lymphoproliferative syndrome (XLP)

Created: 17 Apr 2018, 12:29 p.m.

Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: SH2D1A, GRID_Gene_Symbol: SH2D1A, GRID_Transcript_ENS_Community submitted: ENST00000371139, GRID_Transcript_RefSeq: NM_002351.4, GRID_Transcript_ENS_used_on_Production: ENST00000371139

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