ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000006.11) (NC_000006.12)
Evidence for haploinsufficiency phenotype
PubMed ID Description
25363768 Iossifov et al (2018) performed exome sequencing on a large cohort of families with simplex autism spectrum disorder and analyzed de novo variation in the probands. One individual, from family 14122, was observed to have a heterozygous, de novo frameshifting variant in NEDD9 (GRCh37, chr6:11192636TGAAAACA>T). This variant is present in each NEDD9 isoform and is expected to result in nonsense mediated decay of the transcripts.

Haploinsufficiency phenotype comments:

The EuroEPINOMICS-RES Consortium paper (PMID 25262651, 2014) performed trio exome sequencing on families affected by epileptic encephalopathies, infantile spasms, or Lennox-Gastaut syndrome. One patient (lgsnd37855ajb1) was observed to have de novo variation in NEDD9 that altered two adjacent nucleotides (GRCh37, chr6:11185546T>C and chr6:11185547C>A) in the same codon. The study did not determine whether these variants were present in cis or trans. If they are present on the same allele, this mutational event will replace a glutamic acid residue with a tryptophan residue. However, if the variants are in trans, one of them is predicted to result in a premature stop codon, and is annotated as putative loss of function in the paper's supplemental table.

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity