ClinVar Miner

Submissions for variant NM_018255.4(ELP2):c.1384C>T (p.Arg462Trp)

gnomAD frequency: 0.00002  dbSNP: rs767713084
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000210733 SCV000262928 pathogenic Inborn genetic diseases 2013-09-10 criteria provided, single submitter clinical testing
GeneDx RCV000442926 SCV000525073 likely pathogenic not provided 2016-07-05 criteria provided, single submitter clinical testing The R527W variant in the ELP2 gene has been reported previously as a likely pathogenic variant, in the compound heterozygous state opposite a second ELP2 variant, in two brothers with severe intellectual disability, spastic diplegia, truncal hypotonia, and self-injurious behavior (Cohen et al., 2015). In addition, a different amino acid change at the same residue (R527L), denoted as R426L due to alternative nomenclature, has been reported to be homozygous in a consanguineous family with nonsyndromic intellectual disability (Najmabadi et al., 2011). The R527W variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R527W variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. The R527W variant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded.
OMIM RCV000415555 SCV000493998 pathogenic Intellectual disability, autosomal recessive 58 2011-09-21 no assertion criteria provided literature only
Eurofins Ntd Llc (ga) RCV000442926 SCV000858149 uncertain significance not provided 2017-11-20 flagged submission clinical testing
GenomeConnect - Brain Gene Registry RCV000415555 SCV003931244 not provided Intellectual disability, autosomal recessive 58 no assertion provided phenotyping only Variant classified as Uncertain significance and reported on 08-05-2020 by GeneDx. Assertions are reported exactly as they appear on the patient provided laboratory report. GenomeConnect does not attempt to reinterpret the variant. The IDDRC-CTSA National Brain Gene Registry (BGR) is a study funded by the U.S. National Center for Advancing Translational Sciences (NCATS) and includes 13 Intellectual and Developmental Disability Research Center (IDDRC) institutions. The study is led by Principal Investigator Dr. Philip Payne from Washington University. The BGR is a data commons of gene variants paired with subject clinical information. This database helps scientists learn more about genetic changes and their impact on the brain and behavior. Participation in the Brain Gene Registry requires participation in GenomeConnect. More information about the Brain Gene Registry can be found on the study website - https://braingeneregistry.wustl.edu/.

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