ClinVar Miner

Submissions for variant NM_003482.4(KMT2D):c.14644-3C>G

dbSNP: rs1555186093
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
Labcorp Genetics (formerly Invitae), Labcorp RCV000554613 SCV000636645 uncertain significance Kabuki syndrome 2017-01-18 criteria provided, single submitter clinical testing This sequence change falls in intron 47 of the KMT2D gene. It does not directly change the encoded amino acid sequence of the KMT2D protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). This variant has been shown to arise de novo in an individual affected with Kabuki syndrome (PMID: 24633898). Experimental studies have shown that this variant disrupts splicing, leading to the partial deletion of exon 48 and causing a downstream frameshift and subsequent premature stop codon (PMID: 24633898). In summary, this is a rare intronic change that has been seen in an affected individual and has been shown to disrupt splicing. However, without additional functional and/or genetic data, this variant has been classified as a Variant of Uncertain Significance.
GeneDx RCV003126812 SCV003803385 pathogenic not provided 2022-08-08 criteria provided, single submitter clinical testing Non-canonical splice site variant demonstrated to result in loss of function (Micale L et al., 2014); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 24633898)

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.