Limb disordersGene: TRAF7
Tokita AJHG 103:154-62;2018
Created: 1 Aug 2019, 5:10 p.m. | Last Modified: 1 Aug 2019, 5:10 p.m.
Panel Version: 1.24
Comment on list classification: From Genomics England clinical team - there is evidence of a gene:disease association, however the reported limb differences (distal contractures, altered creases or overlapping digits) do not particularly align with the clinical indication for this panel. One subject in the paper has quite marked radial / ulnar directional deformities of the digits though, therefore amber. Green on Intellectual disability, fetal anomalies, DDG2P panels.
Created: 26 Nov 2019, 12:08 a.m. | Last Modified: 26 Nov 2019, 12:09 a.m.
Panel Version: 1.121
Associated with Cardiac, facial, and digital anomalies with developmental delay (#618164) in OMIM and Developmental Delay, Congenital Anomalies, and Dysmorphic Features in Gene2Phenotype.
PMID: 29961569 - Tokita et al. 2018 - 7 cases. They report missense variants in TRAF7 in seven unrelated individuals referred for clinical exome sequencing. There was substantial phenotypic overlap between individuals, with developmental delay, congenital heart defects, limb and digital anomalies, and dysmorphic features as key features. 6 individuals had de novo variants (absence of paternal DNA in one patient did not allow confirmation of a de novo variant), with four distinct missense changes, including a c.1964G>A (p.Arg655Gln) variant in 4 individuals. The variants affect evolutionarily conserved amino acids and are located in key functional domains.
All 7 subjects had limb and digital anomalies to a variable degree, including variant palmar/digital crease patterns (n = 6) and overlapping toes (n = 5) and clinodactyly (n=3). One subject (Subject 3) had more extensive involvement of the musculoskeletal system including scoliosis with degenerative joint disease, an asymmetric sternum, bilateral avascular necrosis of the hip, tibial malformation, valgus deformity of the ankles, flexion contractures of the hands, and subluxation of multiple joints in the hands and feet.
Created: 7 Aug 2019, 9:24 a.m. | Last Modified: 7 Aug 2019, 9:38 a.m.
Panel Version: 1.37
Gene suggested for the panel by Andrew Wilkie, Oxford University Hospitals NHS Foundation Trust
Sources: Expert list
Created: 1 Aug 2019, 4:19 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Tag missense tag was added to gene: TRAF7.
Gene: traf7 has been classified as Amber List (Moderate Evidence).
Publications for gene: TRAF7 were set to
Phenotypes for gene: TRAF7 were changed from to Cardiac, facial, and digital anomalies with developmental delay, 618164; Developmental Delay, Congenital Anomalies, and Dysmorphic Features
gene: TRAF7 was added gene: TRAF7 was added to Limb disorders. Sources: Expert list Mode of inheritance for gene: TRAF7 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Review for gene: TRAF7 was set to AMBER