Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: F12

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)

NB allelic AR disorder of factor XII deficiency produces Hageman trait

Created: 29 Jun 2018, 1:53 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
hereditary angioedema

Publications

• 16638441
• 17186468

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

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

The missense variants NG_007568.1(NM_000505.3):c.983C>A;p.Thr328Lys and NG_007568.1(NM_000505.3):c.983C>G;p.Thr328Arg affect the threonine residue at position 328 of the protein.1, 2 The p.Thr328Lys variant accounts for the large majority of variant-positive cases reported to date. p.Thr328Lys has been described in patients/families from various ethnic backgrounds. In addition to the two missense variants, one deletion and one duplication have been reported in single families. The NG_007568.1(NM_000505.3):c.971_1018+24del;p.Lys324_Ala340delinsThr variant is a deletion of 72 base pairs (bp). As with the missense variants, the duplication and the deletion affect the proline-rich region

Created: 3 Jul 2018, 11:29 a.m.

Comment on list classification: Changed Amber to Green from external expert review and further publications to support gene-disease association. To date, four disease-causing variants in F12 have been reported .

Created: 3 Jul 2018, 11:26 a.m.

Contrary to HAE types 1 and 2, HAE type 3 occurs mainly in women and attacks are often associated with increased estrogen levels (pregnancy, oral contraception, hormonal replacement therapy).

Created: 3 Jul 2018, 11:24 a.m.

Comment on mode of pathogenicity: added Mode of Pathogenicity as suggested by external expert review

Created: 3 Jul 2018, 10:47 a.m.

Comment on publications: added publications suggested from external expert review to support upgrading of the gene to Green

Created: 3 Jul 2018, 10:46 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 supplied by GRID. GRID Gene Symbol HGNC PanelApp check: F12, GRID_Gene_Symbol: F12, GRID_Transcript_ENS_Community submitted: ENST00000253496, GRID_Transcript_RefSeq: NM_000505.3, GRID_Transcript_ENS_used_on_Production: ENST00000253496

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