ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000009.11) (NC_000009.12)
Evidence for haploinsufficiency phenotype
PubMed ID Description
25055870 In the Georgieva et al 2014 study published in Human Mol Gen, a 188kb deletion CNV (hg19 genome build) was detected by microarray analysis. Classified as de novo in one individual with bipolar affective disorder. This is not a whole gene deletion, as only the 1st noncoding exon of the longest transcript (UCSC genome browser) was deleted. Although de novo, presently, this is not a well-recognized CNV in bipolar disorder or schizophrenia. Also the authors make the point that overall de novo CNVs tended to be smaller in biopolar disorder cohort vs. schizophrenia and therefore may be less pathogenic.

Haploinsufficiency phenotype comments:

ELAVL2 encodes a neuron-specific RNA-binding protein, and is not as yet described as an OMIM morbid gene. Further, it is considered a susceptibility gene for schizophrenia and to date, whole gene deletions have not been reported. Thus far, few studies have been cited in the literature, HGMD, and locus specific autism databases. In population specific databases, 2 LoF variants were reported in gnomAD (one of them being a low confidence call on exome sequencing). Additional studies: PMID: 25363768: In the Iossifov et al 2014 study, ELAVL2 was not a recurrently hit ASD gene on whole exome sequencing from the Simons Simplex Collection (~2500 affected trios or quads sequenced). Iossifov et al reported a de novo deletion of 7 bps resulting in a frameshift change in ELAVL2 (Supp Table 2) in one family (female proband) but details of the clinical phenotype were not provided. Listed as ?DM variant class in HGMD and not previously reported in gnomAD. PMID: 21674006: Yamanda et al 2011, identified a SNP through genotyping in intron 1 of this gene from GWAS studies in a Japanese cohort with a significant p-value ( (p?=?0.00087,1,012 case-control samples). However this gene is considered a susceptibility gene for schizophrenia, and the variant described here is listed as a disease polymorphism in HGMD. They also performed RT PCR studies for mRNA levels for this gene in schizophrenia, bipolar disorder and control post mortem brains and expression levels were no different between the 3 sample sets PMID: 27479843 In Lelieveld et al., 2016 a meta-analysis of over 2000 trio exomes flagged about 10 new genes for intellectual disability, however ELAVL2 was not one of them. A missense de novo change (supp table 2) was reported in one individual from this cohort in this gene but no phenotype details provided.

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

Triplosensitivity phenotype comment:

To date, whole gene duplications of ELAVL2 have not been reported.