ClinVar Miner

Submissions for variant NM_001375380.1(EBF3):c.625C>T (p.Arg209Trp)

dbSNP: rs779003155
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001266965 SCV001445146 likely pathogenic Inborn genetic diseases 2016-12-28 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV001821145 SCV002064338 likely pathogenic not provided 2019-02-22 criteria provided, single submitter clinical testing DNA sequence analysis of the EBF3 gene demonstrated a sequence change, c.625C>T, in exon 7 that results in an amino acid change, p.Arg209Trp. This is a novel sequence change that is not present in the population databases (ExAC, gnomAD). The p.Arg209Trp change affects a highly conserved amino acid residue located in the DNA-binding domain of the EBF3 protein where all other missense pathogenic variants have been described to date. The p.Arg209Trp substitution appears to be possibly damaging using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). This variant has previously been described in two symptomatic siblings with ataxia, ID, speech delay, motor developmental delay, seizures where functional studies were performed that demonstrated a likely defect in protein function (Harms et al.,2017). This sequence change is the likely cause of this phenotype, however functional studies have not been performed to prove this conclusively.
GeneDx RCV001821145 SCV002586608 pathogenic not provided 2022-10-21 criteria provided, single submitter clinical testing Published functional studies suggest a damaging effect as R209W results in mislocalization of the EBF3 protein and impaired association with chromatin (Harms et al., 2016); Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 34050706, 32637629, 28017373)
Baylor Genetics RCV000417009 SCV003835415 pathogenic Hypotonia, ataxia, and delayed development syndrome 2021-04-01 criteria provided, single submitter clinical testing
OMIM RCV000417009 SCV000494483 pathogenic Hypotonia, ataxia, and delayed development syndrome 2023-02-23 no assertion criteria provided literature only
NEUROCHILD, Pediatric Research Center RCV000417009 SCV001547520 pathogenic Hypotonia, ataxia, and delayed development syndrome no assertion criteria provided research
GeneReviews RCV000417009 SCV001737499 not provided Hypotonia, ataxia, and delayed development syndrome no assertion provided literature only Reported in 2 unrelated persons

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.