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Gene: SH2B3

Amber List (moderate evidence)

SH2B3 (SH2B adaptor protein 3)
EnsemblGeneIds (GRCh38): ENSG00000111252
EnsemblGeneIds (GRCh37): ENSG00000111252
OMIM: 605093, Gene2Phenotype
SH2B3 is in 5 panels

2 reviews

Catherine Snow (Genomics England)

Red List (low evidence)

Limited evidence of SH2B3 (alson known as LNK) variants associated with Thrombocythaemia. Most reporting on Thrombocythaemia are in adjacent to work on Myeloproliferative neoplasms (MPNs) - these are a heterogenous group of malignant haematological disorder, of which one of the seven diagnostic entities is Essential Thrombocythaemia.
• PMID 20404132 identifies a patient with thrombocythaemia with a somatic variant (E208Q) in SH2B3 when investigating patients with myeloproliferative neoplasms the patient did not have the known JAK2 (V617F) somatic variant. The role of CALR had not been discovered at this time
• PMID: 27237057 Aimed to discover new variants associated with familial forms of MPN's, 26 members from five families sequenced with at least two members affected by MPN. A proband who had primary myelofibrosis phenotype had the E208Q SH2B3 variant and a CALR variant (p.L367fs*46) were identified. The probands daughter had a thrombocythaemia phenotype with the same SH2B3 variant and the JAK2 (V617F) variant. Three additional family members had the SH2B3 variant but no reported associated phenotypes. Although the E208Q SH2B3 variant is germline there is not sufficient evidence that this variant causes a thrombocythaemia phenotype.
• PMID 27716218 also identified variant E208Q in SH2B3 and concluded it as a germline variant. Two unrelated families each had two family members with MPNs and the E208Q in SH2B3 variant. Only 2/4 with MPNs had thrombocythaemia all had the JAK2 (V617F) variant, the authors concluded that it appears unlikely that SH2B3 alterations may act as driver mutations in MPNs.
Therefore rating SH2B3 as Amber as although germline variants have been discovered the Thromobcythaemia phenotype has only been observed when accompanied with additional known somatic variants in JAK2/CALR
Created: 28 Sep 2020, 3:43 p.m. | Last Modified: 28 Sep 2020, 4:24 p.m.
Panel Version: 0.8

Mode of inheritance


Arina Puzriakova (Genomics England Curator)

This gene has been added to the panel on the recommendation of GMS specialist disease group experts. Rating Amber as only somatic variants are reported in this gene.
Created: 20 Aug 2020, 2:55 p.m. | Last Modified: 20 Aug 2020, 2:55 p.m.
Panel Version: 0.1

Mode of inheritance


Mode of Inheritance
  • Expert Review Amber
  • Thrombocythemia, somatic, 187950
Clinvar variants
Variants in SH2B3
Panels with this gene

History Filter Activity

30 Sep 2020, Gel status: 2

Set mode of inheritance

Arina Puzriakova (Genomics England Curator)

Mode of inheritance for gene: SH2B3 was changed from Unknown to Other

20 Aug 2020, Gel status: 2

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag somatic tag was added to gene: SH2B3.

20 Aug 2020, Gel status: 2

Created, Added New Source, Set mode of inheritance, Set Phenotypes

Arina Puzriakova (Genomics England Curator)

gene: SH2B3 was added gene: SH2B3 was added to Thrombocythaemia. Sources: NHS GMS,Expert Review Amber Mode of inheritance for gene: SH2B3 was set to Unknown Phenotypes for gene: SH2B3 were set to Thrombocythemia, somatic, 187950