Haematological malignancies cancer susceptibility

Gene: DNAJC21

The rating of this gene has been updated following NHS Genomic Medicine Service approval.

Created: 3 Mar 2022, 10:30 a.m. | Last Modified: 3 Mar 2022, 10:30 a.m.

Panel Version: 2.23

Comment on list classification: New gene added by Kiran Tawana (Addenbrooke's Hospital, Cambridge) with a Green expert review rating.

Biallelic variants in the DNAJC21 gene are associated with bone marrow failure syndrome-3 (MIM# 617052). At least 15 individuals reported in literature (PMIDs: 27346687; 28062395; 29146883; 29700810), of which only one developed acute myeloid leukaemia (AML-M7), at the age of 12 years (P3 in PMID: 27346687). However, it should be considered that the remaining cases were all children (14 mo - 14 yrs of age) and so the risk of malignancy later in life remains.

BMF syndromes can be associated with an increased cancer risk, and in parallel with the Green expert review, DNAJC21 will be flagged for GMS review to assess whether there is substantial evidence to rate this gene Green on this panel.

Created: 2 Feb 2021, 3:04 p.m. | Last Modified: 2 Feb 2021, 3:04 p.m.

Panel Version: 2.7

Green List (high evidence)

Sources: Literature

Created: 29 Jan 2021, 12:11 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
bone marrow failure; AML; developmental delay; pancreatic insufficiency, overlap with SBDS

Publications

• PMID: 27346687
• PMID: 29700810