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Genetic epilepsy syndromes

Gene: TRAF7

Amber List (moderate evidence)

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

4 reviews

Tracy Lester (Genetics laboratory, Oxford UK)

Green List (high evidence)

Limited evidence: PMID 29961569 reported 7 patients with a similar disorder but only two had seizures (with a further one with possible absence seizures)
Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.
Panel Version: 1.188

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Cardiac, facial, and digital anomalies with developmental delay, 618164

Publications

Rebecca Foulger (Genomics England curator)

I don't know

As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that this gene can remain as Amber: TRAF7 is Green on the Intellectual disability and Paediatric disorders panels, which would be appropriate for the presenting phenotype.
Created: 15 Aug 2019, 8:10 a.m. | Last Modified: 15 Aug 2019, 8:10 a.m.
Panel Version: 1.223
Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: Alison Callaway and John Taylor. Suggested gene rating: Green.
Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.
Panel Version: 1.189
Comment on list classification: Kept rating as Amber following external review by Konstantinos Varvagiannis: currently seizures are not a consistent phenotype (2/7 patients in PMID:29961569). Disease confidence rating in Gene2Phenotype is 'probable' for the disorder: Developmental Delay Congenital Anomalies and Dysmorphic Features. Added watchlist tag as further cases of seizures/epilepsy are required for a Green rating.
Created: 2 Jul 2019, 3:31 p.m. | Last Modified: 2 Jul 2019, 3:31 p.m.
Panel Version: 1.109
PMID 29961569: Tokita et al, 2018 report TRAF7 missense variants in seven unrelated individuals. Seizures reported in two patients, plus 'possible absence seizures' reported in patient 6.
Created: 2 Jul 2019, 3:28 p.m. | Last Modified: 2 Jul 2019, 3:28 p.m.
Panel Version: 1.108
Comment on phenotypes: Updated phenotypes to include new OMIM disorder: MIM:618164 (Cardiac, facial, and digital anomalies with developmental delay).
Created: 14 May 2019, 11:38 a.m.

Sarah Leigh (Genomics England Curator)

Comment when marking as ready: Not associated with phenotype in OMIM or in Gen2Phen. However, OMIM for this gene has not been updated since 04/01/2013. Review from Konstantinos Varvagiannis suggests sufficient evidence exists for TRAF7 to be amber on this panel and possibly green.
Created: 7 Nov 2018, 1:58 p.m.

Konstantinos Varvagiannis (Other)

I don't know

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). Some of these individuals had been investigated in the past for disorders of the Ras-MAPK pathway (CFC, Noonan and Costello syndrome).

Two (or possibly three) of these patients had seizures.

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 epilepsy panel as amber (seizures having been reported in some of the patients).
Sources: Literature, Expert Review
Created: 15 Oct 2018, 3:57 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

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Amber
  • Wessex and West Midlands GLH
  • NHS GMS
Phenotypes
  • Cardiac, facial, and digital anomalies with developmental delay, 618164
  • Global developmental delay
  • Abnormal heart morphology
  • Abnormality of digit
  • Abnormality of limbs
Tags
watchlist
OMIM
606692
Clinvar variants
Variants in TRAF7
Penetrance
unknown
Publications
Panels with this gene

History Filter Activity

15 Aug 2019, Gel status: 2

Entity classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

Gene: traf7 has been classified as Amber List (Moderate Evidence).

6 Aug 2019, Gel status: 2

Added New Source

Rebecca Foulger (Genomics England curator)

Source Wessex and West Midlands GLH was added to TRAF7.

6 Aug 2019, Gel status: 2

Added New Source

Rebecca Foulger (Genomics England curator)

Source NHS GMS was added to TRAF7.

2 Jul 2019, Gel status: 2

Added Tag

Rebecca Foulger (Genomics England curator)

Tag watchlist tag was added to gene: TRAF7.

2 Jul 2019, Gel status: 2

Entity classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

Gene: traf7 has been classified as Amber List (Moderate Evidence).

14 May 2019, Gel status: 2

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for gene: TRAF7 were changed from Global developmental delay; Abnormal heart morphology; Abnormality of digit; Abnormality of limbs to Cardiac, facial, and digital anomalies with developmental delay, 618164; Global developmental delay; Abnormal heart morphology; Abnormality of digit; Abnormality of limbs

11 Dec 2018, Gel status: 2

Panel promoted to version 1.0

Sarah Leigh (Genomics England Curator)

Konstantinos Varvagiannis: PMID: 29961569 reports on 7 un

7 Nov 2018, Gel status: 2

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

Gene: traf7 has been classified as Amber List (Moderate Evidence).

7 Nov 2018, Gel status: 2

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

Gene: traf7 has been classified as Amber List (Moderate Evidence).

15 Oct 2018, Gel status: 0

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

Konstantinos Varvagiannis (Other)

gene: TRAF7 was added gene: TRAF7 was added to Genetic Epilepsy Syndromes. Sources: Literature,Expert Review Mode of inheritance for gene: TRAF7 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: TRAF7 were set to 29961569; 27479843; 28135719; 25363760; 25961944 Phenotypes for gene: TRAF7 were set to Global developmental delay; Abnormal heart morphology; Abnormality of digit; Abnormality of limbs Penetrance for gene: TRAF7 were set to unknown Review for gene: TRAF7 was set to AMBER