Submissions for variant NM_003482.4(KMT2D):c.5124_5125del (p.Arg1709fs)

dbSNP: rs886043506

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000725909	SCV000340456	pathogenic	not provided	2016-03-11	criteria provided, single submitter	clinical testing
Baylor-Hopkins Center for Mendelian Genomics, Johns Hopkins University School of Medicine	RCV000400113	SCV000583533	likely pathogenic	Kabuki syndrome 1		criteria provided, single submitter	research
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV000400113	SCV001369827	pathogenic	Kabuki syndrome 1	2020-01-30	criteria provided, single submitter	clinical testing	This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PM2,PP5.
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	RCV000400113	SCV002512429	pathogenic	Kabuki syndrome 1	2022-01-27	criteria provided, single submitter	clinical testing	ACMG classification criteria: PVS1 very strong, PS4 supporting, PM2 moderate
Athena Diagnostics Inc	RCV000725909	SCV002817306	pathogenic	not provided	2020-09-11	criteria provided, single submitter	clinical testing	This variant is expected to result in the loss of a functional protein This variant has been previously identified in Kabuki patients and occurred de novo in an individual tested at Athena Diagnostics, who had clinical features associated with the KMT2D gene (PMID: 29255178, 22126750). This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org).This observation is not an independent occurrence and has been identified in the same individual by RCIGM, the other laboratory participating in the GEMINI study.
Ambry Genetics	RCV002519267	SCV003548712	pathogenic	Inborn genetic diseases	2020-11-18	criteria provided, single submitter	clinical testing	The c.5124_5125delAC (p.R1709Hfs*25) alteration, located in coding exon 21 of the KMT2D gene, consists of a deletion of 2 nucleotides from position 5124 to 5125, causing a translational frameshift with a predicted alternate stop codon after 25 amino acids. Frameshift alterations are typically deleterious in nature (Richards, 2015). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Based on data from the Genome Aggregation Database (gnomAD), the KMT2D c.5124_5125delAC alteration was not observed, with coverage at this position. This alteration has been reported once in two separate cohorts of patients with a clinical diagnosis of Kabuki syndrome (Banka, 2012; Sobreira, 2017). Based on the available evidence, this alteration is classified as pathogenic.