Submissions for variant NM_001429.4(EP300):c.6627_6638del (p.Asn2209_Gln2213delinsLys)

dbSNP: rs587778256

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001722282	SCV000564967	benign	not provided	2019-01-17	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 29506490, 33337535)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000490777	SCV001021025	likely benign	Rubinstein-Taybi syndrome due to EP300 haploinsufficiency	2024-01-23	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV000490777	SCV001440272	likely benign	Rubinstein-Taybi syndrome due to EP300 haploinsufficiency	2019-01-01	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001722282	SCV002496752	benign	not provided	2024-08-01	criteria provided, single submitter	clinical testing	EP300: BS1, BS2
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	RCV002252064	SCV002522978	benign	See cases	2022-01-14	criteria provided, single submitter	clinical testing	ACMG classification criteria: BS1, BS2
Ambry Genetics	RCV002518550	SCV003684812	likely benign	Inborn genetic diseases	2021-07-23	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
ITMI	RCV000120716	SCV000084878	not provided	not specified	2013-09-19	no assertion provided	reference population
Fundacion Rioja Salud, Center for Biomedical Research (CIBIR)	RCV000490777	SCV000297727	pathogenic	Rubinstein-Taybi syndrome due to EP300 haploinsufficiency	2016-07-01	flagged submission	research
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001722282	SCV001962796	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001722282	SCV001973947	likely benign	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001722282	SCV002035853	likely benign	not provided		no assertion criteria provided	clinical testing
Dr. med. U. Finckh, Human Genetics, Eurofins MVZ	RCV000490777	SCV004037313	uncertain significance	Rubinstein-Taybi syndrome due to EP300 haploinsufficiency	2022-10-20	flagged submission	clinical testing	This EP300 variant deletes 12 nucleotides leading to an inframe deletion of codons 2209-2213 and insertion of 1 Lysine. It has been described occurring de novo in patients with Rubinstein-Taybi syndrome (PMID: 29506490, 33337535) but also is present in approx. 0.6% of the european general population. Either the variant was found randomly and without causal relationship in affected patients or it predisposes - seeming less likely - to a low-penetrance / variable-expression form of the disease, possibly influenced by additional factors. Internal data: Heterozygous in a proband with early childhood autism spectrum disorder not displaying any other obvious similarities to Rubinstein-Taybi syndrome. Subsequently, the variant was also detected in the unaffected father. We classify the variant as uncertain.
PreventionGenetics, part of Exact Sciences	RCV003920007	SCV004735768	likely benign	EP300-related disorder	2019-07-26	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).