ClinVar Miner

Submissions for variant NM_017780.4(CHD7):c.6079C>T (p.Arg2027Ter) (rs886040995)

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
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia RCV000258088 SCV000328344 pathogenic CHARGE association 2016-09-05 criteria provided, single submitter clinical testing
GeneDx RCV000330520 SCV000329270 pathogenic not provided 2016-09-15 criteria provided, single submitter clinical testing The R2027X nonsense variant in the CHD7 gene has been reported previously as a de novo occurrence in four patients in association with CHARGE syndrome (Jongmans et al., 2006; Janssen et al., 2012; Busa et al., 2016). Approximately 45% of CHD7 pathogenic variants are nonsense changes predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay (Janssen et al., 2012; Zentner et al, 2010). Additionally, the R2027X variant was not observed in approximately 6,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Therefore, the presence of the R2027X pathogenic variant is consistent with a diagnosis of CHARGE syndrome
Invitae RCV000258088 SCV000755717 pathogenic CHARGE association 2019-10-26 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg2027*) in the CHD7 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported de novo in individuals affected with CHARGE (PMID: 16155193, 22461308, 27061523). ClinVar contains an entry for this variant (Variation ID: 267435). Loss-of-function variants in CHD7 are known to be pathogenic (PMID: 22461308, 25077900). For these reasons, this variant has been classified as Pathogenic.
Broad Institute Rare Disease Group, Broad Institute RCV000258088 SCV000786713 pathogenic CHARGE association criteria provided, single submitter research The heterozygous p.Arg227Ter variant was identified by our study in one individual with CHARGE syndrome. The p.Arg227Ter variant is believed to be pathogenic based on numberous reports by other laboratories in the literature and databases.
Victorian Clinical Genetics Services,Murdoch Childrens Research Institute RCV000258088 SCV001244805 pathogenic CHARGE association 2018-04-26 criteria provided, single submitter clinical testing A heterozygous nonsense variant, NM_017780.3(CHD7):c.6079C>T, has been identified in exon 30 of 38 in the CHD7 gene. The variant is predicted to result in a premature stop codon at position 2027 of the protein, NP_060250.2(CHD7):p.(Arg2027*). The variant is predicted to result in loss of protein function either through truncation (downstream functional domains would be affected) or nonsense-mediated decay, which is a reported mechanism of pathogenicity for this gene. The variant is absent in population databases (gnomAD, dbSNP, 1000G) and has been previously described as pathogenic in multiple individuals with CHARGE syndrome (ClinVar, Jongmans et al., (2016), Busa et al., (2016)). Based on the information available at the time of curation, this variant has been classified as PATHOGENIC.
SBielas Lab, Department of Human Genetics,University of Michigan RCV000258088 SCV000680052 pathogenic CHARGE association 2017-10-27 no assertion criteria provided research
University of Washington Center for Mendelian Genomics, University of Washington RCV000258088 SCV001197958 likely pathogenic CHARGE association no assertion criteria provided research

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.