ClinVar Miner

Submissions for variant NM_001367624.1(ZNF469):c.6444del (p.Gln2149fs) (rs886044697)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000484202 SCV000345953 pathogenic not provided 2016-09-15 criteria provided, single submitter clinical testing
GeneDx RCV000484202 SCV000568248 likely pathogenic not provided 2016-11-15 criteria provided, single submitter clinical testing The normalsequence with the base that is deleted in brackets is: TGGGGGG[delG]CAGC.The c.6360delG likely pathogenic variant has been identified in the ZNF469 gene. This variant has previously beenreported in the homozygous state in an individual with reduced brittle cornea syndrome (BCS) (reported asc.6444delG p.Gln2149Serfs*51 due to inclusion of intronic sequence) (Rohrbach et al., 2103). This variant causes ashift in reading frame starting at codon Glutamine 2121, changing it to a Serine, and creating a premature stop codonat position 51 of the new reading frame, denoted p.Gln2121SerfsX51. The c.6360delG variant is expected to result inan abnormal, truncated protein product, with the last 1805 amino acids being replaced by 50 incorrect amino acids.Other downstream frameshift variants in the ZNF469 gene have been reported in HGMD in association with BCS(Stenson et al., 2014). Furthermore, the c.6360delG variant was not observed in approximately 2,200 individuals ofEuropean and African American ancestry in the NHLBI Exome Sequencing Project (average read depth 6X).In summary, c.6360delG in the ZNF469 gene is expected to be pathogenic, as loss of function variants in this geneare strongly associated with this phenotype.

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.