Inherited phaeochromocytoma and paraganglioma excluding NF1
Gene: DNMT3A

DNMT3A (DNA methyltransferase 3 alpha)
EnsemblGeneIds (GRCh38): ENSG00000119772
EnsemblGeneIds (GRCh37): ENSG00000119772
OMIM: 602769, Gene2Phenotype
DNMT3A is in 8 panels

3 reviews

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Created: 10 Dec 2025, 5:30 p.m. | Last Modified: 10 Dec 2025, 5:30 p.m.

Panel Version: 3.8

Created: 10 Dec 2025, 5:30 p.m.
Last Modified: 10 Dec 2025, 5:30 p.m.
Panel version: 3.8

Sarah Leigh (Genomics England Curator)

Green List (high evidence)

Four different DNMT3A variants have so far been associated with carotid paragangliomas in a total of ten cases as part of a syndrome. All of the variants are located within the proline-tryptophan-tryptophan-proline (PWWP) domain of DNMT3A (PMID: 29740169; 33182397; 39166703). De novo occurrence of the DNMT3A variant was proven in one case, one variant was inherited from a mother in another case, three were somatic and the inheritance could not be established in five cases (PMID: 29740169; 33182397; 39166703). The DNMT3A variants had a gain of function mechanism, resulting in hypermethylation of polycomb-marked developmental genes and altered chromatin binding specificity (PMID: 39166703).
Created: 31 Mar 2025, 5:30 p.m. | Last Modified: 31 Mar 2025, 5:30 p.m.

Panel Version: 3.6

Comment on phenotypes: The patient reported in PMID: 39166703 had Heyn-Sproul-Jackson syndrome (OMIM: 618724), with recurrent carotid paragangliomas.
Created: 31 Mar 2025, 4:03 p.m. | Last Modified: 31 Mar 2025, 4:03 p.m.

Panel Version: 3.4

Created: 31 Mar 2025, 4:03 p.m.
Last Modified: 31 Mar 2025, 4:03 p.m.
Panel version: 3.6

Dmitrijs Rots (Children's Clinical University Hospital)

Green List (high evidence)

Over multiple case reports, missense variants in DNMT3A PWWP domain seem to be associated with paragangliomas (PMID:39166703).
Sources: Literature
Created: 27 Dec 2024, 10:48 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Publications

39166703

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

Created: 27 Dec 2024, 10:48 a.m.

Panel version: 3.1

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Sources

Expert Review Green
NHS GMS

Phenotypes

Heyn-Sproul-Jackson syndrome, OMIM:618724

OMIM

602769

Clinvar variants

Variants in DNMT3A

Penetrance

unknown

Publications

Mode of Pathogenicity

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

Panels with this gene

History Filter Activity

10 Dec 2025, Gel status: 3

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: DNMT3A were changed from Heyn-Sproul-Jackson syndrome, OMIM: 618724 to Heyn-Sproul-Jackson syndrome, OMIM:618724

10 Dec 2025, Gel status: 3

Removed Tag

Arina Puzriakova (Genomics England Curator)

Tag Q1_25_ promote_green was removed from gene: DNMT3A.

10 Dec 2025, Gel status: 3

Added New Source, Added New Source, Status Update

Arina Puzriakova (Genomics England Curator)

Source NHS GMS was added to DNMT3A. Source Expert Review Green was added to DNMT3A. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

31 Mar 2025, Gel status: 2