Total submissions: 7
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, |
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. |
Gene |
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, |
RCV000417009 | SCV001547520 | pathogenic | Hypotonia, ataxia, and delayed development syndrome | no assertion criteria provided | research | ||
Gene |
RCV000417009 | SCV001737499 | not provided | Hypotonia, ataxia, and delayed development syndrome | no assertion provided | literature only | Reported in 2 unrelated persons |