BAD Oncology Monarch id/name
|25284784||This study (Dong et al, 2014) examined de novo insertions and deletions in 787 families included in the Simons Simplex Collection. A de novo frameshift variant, c.1352_1355del, p.(Phe451Leufs*14), in TNRC6B was detected and confirmed in a male proband.|
|25363768||This study (Iossifov et al, 2014) used exome sequencing to identify de novo variants in >2500 simplex ASD families from the Simons Simplex Collection. Two de novo variants were detected in two independent male probands (1 frameshift - same as Dong et al, and 1 nonsense, NM_015088.2:c.2479C>T, p.Gln827*) (Supplementary Table 2).|
|27479843||Lelieveld et al (2016) identified de novo variants from exomes of 2,104 intellectual disability trios (RUMC cohort). A confirmed de novo nonsense variant, NM_001162501.1:c.3343C>T, p.R1115* was detected in TNRC6B. Of note, this variant is observed in gnomAD (1 European [non-Finnish] allele out of 249190, frequency 4.01e-6) as of June 2019.|
Loss-of function de novo sequence variants in TNRC6B have been detected in probands with autism spectrum disorder and intellectual disability (at least 8 de novo independent variants). One larger deletion (66kb) intragenic to TNRC6B has also been detected in an individual with developmental delay [inheritance unknown, Decipher patient 346766]. Loss-of-function variants are also present in control individuals included in the gnomAD database, but at a frequency lower than expected for the gene (o/e=0.1). The gnomAD pLI for this gene is 1.0 and the DECIPHER HI index is 5.61%, suggesting this gene may be intolerant to loss-of-function variation. Additional references: PMID: 28191889 - In this study, Stessman et al (2017) sequenced 208 candidate genes from >11,730 cases with autism and developmental disabilities and >2,867 controls. A confirmed de novo frameshift variant, c.754dup, p.Glu252Glyfs*3, was detected in a proband from the AGRE cohort. Additional loss-of-function variants are included in Supplementary table 11 with inheritance unknown. PMID: 30564305 - In this study, Guo et al (2018) used targeted gene sequencing to investigate individuals included in the Autism Clinical and Genetic Resources in China (Phase 2). Two de novo loss-of-function variants were detected in TNRC6B. The first was a nonsense variant, c.1879C>T, p.Q627* and the second was a deletion, c.4892del, p.Trp1625Glyfs*40. PMID: 30504930 - In this study, Guo et al (2018) used whole genome sequencing to investigate 108 simplex and multiplex autism spectrum disorder families from the SAGE cohort. A splice site mutation (NM_001024843.1:c.46-2A>G), was detected in a proband and his father. Phenotype information for the father was not presented. This variant is also present in the gnomAD population dataset (0.0046% MAF). PMID: 29463886 - In this study, Eising et al (2018) complete whole genome sequencing of 19 childhood apraxia of speech (CAS) trios and detected a de novo TNRC6B variant (c.2040G>A, p.W680*) in one proband with CAS and autism spectrum disorder (Case 15).
No whole gene duplications reported at this time