Genes in panel
STRs in panel
Prev Next

Primary immunodeficiency

Gene: SH2D1A

Green List (high evidence)

SH2D1A (SH2 domain containing 1A)
EnsemblGeneIds (GRCh38): ENSG00000183918
EnsemblGeneIds (GRCh37): ENSG00000183918
OMIM: 300490, Gene2Phenotype
SH2D1A is in 7 panels

5 reviews

Kimberly Gilmour (Great Ormond Street Hopsital)

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

Tracy Briggs (Manchester Genomic Medicine Centre)

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

Sophie Hambleton (Newcastle University)

Green List (high evidence)

Eleanor Williams (Genomics England Curator)

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

Louise Daugherty (Genomics England Curator)

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.

Details

Mode of Inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Sources
  • Expert Review Green
  • Other
  • NHS GMS
  • North West GLH
  • London North GLH
  • IUIS Classification February 2018
  • Victorian Clinical Genetics Services
  • ESID Registry 20171117
  • GRID V2.0
  • GOSH PID v.8.0
Phenotypes
  • Lymphoproliferative syndrome, X-linked, 1 308240
  • Lymphoproliferative syndrome, X-linked, 1 (XLP1)
  • X-linked lymphoproliferative syndrome (XLP)
  • EBV, HLH, Lymphoproliferation, Aplastic anaemia, Lymphoma. Hypogammaglobulinemia, Absent iNKT cells
  • Diseases of Immune Dysregulation
OMIM
300490
Clinvar variants
Variants in SH2D1A
Penetrance
None
Publications
Panels with this gene

History Filter Activity

14 Oct 2020, Gel status: 3

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: sh2d1a has been classified as Green List (High Evidence).

13 Oct 2020, Gel status: 1

Added New Source, Set publications, Status Update

Eleanor Williams (Genomics England Curator)

Source Other was added to SH2D1A. Publications for gene SH2D1A were updated from 9771704; 10556288; 10598819; 10694488; 11049992; 29670631; 9774102 to 21119115; 29670631; 10556288; 9774102; 11049992; 10598819; 9771704; 10694488; 25085526; 31754776 Rating Changed from Green List (high evidence) to Red List (low evidence)

17 Sep 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to SH2D1A.

17 Sep 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source North West GLH was added to SH2D1A.

17 Sep 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source London North GLH was added to SH2D1A.

12 Jul 2018, Gel status: 4

Panel promoted to version 1.0

Louise Daugherty (Genomics England Curator)

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.

1 Jul 2018, Gel status: 4

Set penetrance

Louise Daugherty (Genomics England Curator)

Phenotypes for gene SH2D1A were set to Lymphoproliferative syndrome, X-linked, 1 308240, Lymphoproliferative syndrome, X-linked, 1 (XLP1), X-linked lymphoproliferative syndrome (XLP), EBV, HLH, Lymphoproliferation, Aplastic anaemia, Lymphoma. Hypogammaglobulinemia, Absent iNKT cells, Diseases of Immune Dysregulation

26 Jun 2018, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

IUIS Classification February 2018 was added to SH2D1A. Panel: Primary immunodeficiency disorders

26 Jun 2018, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

Victorian Clinical Genetics Services was added to SH2D1A. Panel: Primary immunodeficiency disorders

13 Jun 2018, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: sh2d1a has been classified as Green List (High Evidence).

13 Jun 2018, Gel status: 3

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: SH2D1A were set to 9771704; 10556288; 10598819; 10694488; 11049992; 29670631; 9774102

1 May 2018, Gel status: 3

Gene classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

1 May 2018, Gel status: 2

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for SH2D1A were set to Lymphoproliferative syndrome, X-linked, 1 308240; Lymphoproliferative syndrome, X-linked, 1 (XLP1); X-linked lymphoproliferative syndrome (XLP)

1 May 2018, Gel status: 2

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for SH2D1A were set to Lymphoproliferative syndrome, X-linked 1308240; Lymphoproliferative syndrome, X-linked, 1 (XLP1); X-linked lymphoproliferative syndrome (XLP)

19 Apr 2018, Gel status: 2

Gene classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

This gene has been classified as Amber List (Moderate Evidence).

17 Apr 2018, Gel status: 1

Added New Source, Set penetrance

Louise Daugherty (Genomics England Curator)

ESID Registry 20171117 was added to SH2D1A. Panel: Primary immunodeficiency disorders Phenotypes for gene SH2D1A were set to Lymphoproliferative syndrome, X-linked, 1, Lymphoproliferative syndrome, X-linked, 1 (XLP1), X-linked lymphoproliferative syndrome (XLP)

17 Apr 2018, Gel status: 1

Set penetrance

Louise Daugherty (Genomics England Curator)

Phenotypes for gene SH2D1A were set to Lymphoproliferative syndrome, X-linked, 1, Lymphoproliferative syndrome, X-linked, 1 (XLP1)

17 Apr 2018, Gel status: 1

Added New Source, Set penetrance

Louise Daugherty (Genomics England Curator)

GRID V2.0 was added to SH2D1A. Panel: Primary immunodeficiency disorders Phenotypes for gene SH2D1A were set to Lymphoproliferative syndrome, X-linked, 1, Lymphoproliferative syndrome, X-linked, 1 (XLP1)

6 Apr 2018, Gel status: 1

Clear Sources

Louise Daugherty (Genomics England Curator)

SH2D1A Source: GOSH PID 20171191 was removed from gene: SH2D1A

6 Apr 2018, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

GOSH PID v.8.0 was added to SH2D1A. Panel: Primary immunodeficiency disorders

29 Mar 2018, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

SH2D1A was added to Primary immunodeficiency disorders panel. Sources: GOSH PID 20171191

29 Mar 2018, Gel status: 1

Created

Louise Daugherty (Genomics England Curator)

SH2D1A was created by Louise Daugherty