ClinVar Miner

Submissions for variant NM_133433.4(NIPBL):c.7168G>A (p.Ala2390Thr) (rs587784036)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000146717 SCV000194033 pathogenic Cornelia de Lange syndrome 1 2013-02-08 criteria provided, single submitter clinical testing
GeneDx RCV000494480 SCV000582781 likely pathogenic not provided 2017-05-05 criteria provided, single submitter clinical testing The A2390T variant has been reported de novo in a patient with features of Cornelia de Lange syndrome including a limb reduction defect (Gillis et al., 2004). The A2390T variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The A2390T 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. In silico analysis predicts this variant is probably damaging to the protein structure/function. In summary, this variant is likely pathogenic.
Invitae RCV000146717 SCV000944779 pathogenic Cornelia de Lange syndrome 1 2018-09-19 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 2390 of the NIPBL protein (p.Ala2390Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in individuals affected with classical Cornelia de Lange syndrome (PMID: 15318302, Invitae) and as a somatic mosaic in an individual affected with mild Cornelia de Lange syndrome (PMID: 23505322). ClinVar contains an entry for this variant (Variation ID: 159223). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). For these reasons, this variant has been classified as Pathogenic.

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.