Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_006180.6(NTRK2):c.6_8delGTC(p.Ser3del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00000186 in 1,612,476 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
NTRK2 (HGNC:8032): (neurotrophic receptor tyrosine kinase 2) This gene encodes a member of the neurotrophic tyrosine receptor kinase (NTRK) family. This kinase is a membrane-bound receptor that, upon neurotrophin binding, phosphorylates itself and members of the MAPK pathway. Signalling through this kinase leads to cell differentiation. Mutations in this gene have been associated with obesity and mood disorders. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]
Review Status: criteria provided, single submitter
Collection Method: clinical testing
This variant has not been reported in the literature in individuals affected with NTRK2-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant, c.6_8del, results in the deletion of 1 amino acid(s) of the NTRK2 protein (p.Ser3del), but otherwise preserves the integrity of the reading frame. -