ClinVar Miner

Submissions for variant NM_003482.4(KMT2D):c.15565G>A (p.Gly5189Arg)

dbSNP: rs1555185701
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Human Genetics, Inc, Center for Human Genetics, Inc RCV000659824 SCV000781687 uncertain significance Kabuki syndrome 1 2016-11-01 criteria provided, single submitter clinical testing
Invitae RCV001060415 SCV001225102 likely pathogenic Kabuki syndrome 2019-05-13 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 5189 of the KMT2D protein (p.Gly5189Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with clinical features of Kabuki syndrome, in at least one of whom it was found de novo (PMID: 27302555, 23913813, 30107592, Invitae). ClinVar contains an entry for this variant (Variation ID: 547502). This variant has been reported to affect KMT2D protein function (PMID: 30107592). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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