Intellectual disability
Gene: TRAF7

TRAF7 (TNF receptor associated factor 7)
EnsemblGeneIds (GRCh38): ENSG00000131653
EnsemblGeneIds (GRCh37): ENSG00000131653
OMIM: 606692, Gene2Phenotype
TRAF7 is in 8 panels

3 reviews

Louise Daugherty (Genomics England Curator)

As a result of watchlist tag audit the watchlist tag was removed from TRAF7- this is now a green gene with sufficient evidence/review
Created: 13 Jan 2020, 4:18 p.m. | Last Modified: 13 Jan 2020, 4:18 p.m.

Panel Version: 3.0

Created: 13 Jan 2020, 4:18 p.m.
Last Modified: 13 Jan 2020, 4:18 p.m.
Panel version: 3.0

Rebecca Foulger (Genomics England curator)

Comment on list classification: Updated rating from Amber to Green following advice from the Genomics England clinical team that the combination of motor and speech delay would be regarded by many clinicians as equivalent to global developmental delay.
Created: 1 Jul 2019, 3:30 p.m. | Last Modified: 1 Jul 2019, 3:30 p.m.

Panel Version: 2.933

Comment on list classification: TRAF7 was added to the panel and rated Green by Konstantinos Varvagiannis based on PMID:29961569 (Tokita et al, 2018) who report four different heterozygous missense mutations in the TRAF7 gene in 7 unrelated patients with MIM:618164. The variants were de novo in at least six of the patients. Motor and/or speech delay were present to a variable degree in 5 of the 5 subjects for whom this outcome could be assessed (The remaining two subjects were 1 week old and 3 weeks old). After discussion with Louise Daugherty, I have rated TRAF7 as Amber: PMID:29961569 assayed motor delay and speech delay as indicators of developmental delay- the authors don't refer to global DD, and motor/speech delay are not directly linked to ID. Additional evidence comes from an ID cohort study (PMID:27479843, Lelieveld et al, 2016) and the DDD study (PMID:28135719). Rated Amber with a 'watchlist' tag, awaiting further evidence.
Created: 14 May 2019, 12:15 p.m.

Comment on publications: PMIDs 25363760 and 25961944 report variants detected in autism patients. This is out of scope of the ID panel, so I have removed these publications from the current list.
Created: 14 May 2019, 11:50 a.m.

TRAF7 is now associated with a disorder in OMIM: Cardiac, facial, and digital anomalies with developmental delay, 618164.
Created: 14 May 2019, 11:47 a.m.

Created: 14 May 2019, 11:47 a.m.

Panel version: 2.818

Konstantinos Varvagiannis (Other)

Green List (high evidence)

PMID: 29961569 reports on 7 unrelated individuals with pathogenic variants in TRAF7. Common features included developmental delay, congenital heart defects, limb and digital anomalies as well as shared facial features (including epicanthal folds, ptosis, abnormal ears, excess nuchal skin). Two (or possibly three) of these patients had seizures. Some of these individuals had been investigated in the past for disorders of the Ras-MAPK pathway (CFC, Noonan and Costello syndrome).

The SNVs reported are missense and occured de novo in all patients for whom parental studies were possible (6 out of 7). A recurrent mutation [p.(Arg655Gln)] was found in 4 of the 7 individuals. One patient was found to harbor a mutation in the mosaic state, as a de novo occurrence.

The variants resulted in reduced activation of ERK1/2 (also known as MAPK3/MAPK1). //

7 individuals with de novo coding variants have previously been reported in large cohorts of patients with intellectual disability (PMIDs : 27479843, 28135719 - DDD study) and/or ASD (25363760, 25961944). One of the individuals from the DDD study had a stopgain variant.

The individuals from these studies are summarized in the denovo-db (http://denovo-db.gs.washington.edu/denovo-db/QueryVariantServlet?searchBy=Gene&target=TRAF7) //

As a result this gene can be considered for inclusion in the ID panel as green (or amber).
Sources: Expert Review, Literature
Created: 15 Oct 2018, 3:52 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Global developmental delay; Abnormal heart morphology; Abnormality of digit; Abnormality of limbs

Publications

Created: 15 Oct 2018, 3:52 p.m.

Panel version: 2.510

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Sources

Expert Review Green

Phenotypes

Cardiac, facial, and digital anomalies with developmental delay, 618164
Global developmental delay
Abnormal heart morphology
Abnormality of digit
Abnormality of limbs

OMIM

606692

Clinvar variants

Variants in TRAF7

Penetrance

unknown

Publications

Panels with this gene

History Filter Activity

13 Jan 2020, Gel status: 3

Removed Tag

Louise Daugherty (Genomics England Curator)

Tag watchlist was removed from gene: TRAF7.

1 Jul 2019, Gel status: 3