Submissions for variant NM_006766.5(KAT6A):c.3385C>T (p.Arg1129Ter)

dbSNP: rs786200960

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000623870	SCV000741647	pathogenic	Inborn genetic diseases	2016-06-28	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001091600	SCV001247733	pathogenic	not provided	2019-01-01	criteria provided, single submitter	clinical testing
Laboratoire de Génétique Moléculaire, CHU Bordeaux	RCV001091600	SCV001468981	pathogenic	not provided		criteria provided, single submitter	clinical testing
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV000167546	SCV002769367	pathogenic	Autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome	2020-10-19	criteria provided, single submitter	clinical testing	Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss-of-function is a known mechanism of disease for this gene. (N) 0107 - This gene is known to be associated with autosomal dominant disease. (N) 0204 - Variant is predicted to result in a truncated protein with more than 1/3 of the protein affected (exon 17 of 17). (P) 0251 - Variant is heterozygous. (N) 0301 - Variant is absent from gnomAD. (P) 0401 - Variant is located in a gene associated with a severe early-onset dominant condition that is intolerant to loss-of-function variants. (P) 0601 - Variant affects at least one well-established (essential) functional domain or motif. The variant is located within the transactivation domain which is essential for normal protein function (PMID: 25728777). (P) 0701 - Comparable variants have very strong previous evidence for pathogenicity. Many other downstream truncating variants have previously been reported as pathogenic (ClinVar, PMID: 30245513). (P) 0801 - Strong previous evidence of pathogenicity in unrelated individuals. The variant has previously been reported as de novo in multiple patients (ClinVar, PMID: 25728775, PMID: 30245513). (P) 1203 - Variant shown to be de novo in proband (parental status confirmed). (P) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign
Invitae	RCV001091600	SCV003440699	pathogenic	not provided	2022-09-07	criteria provided, single submitter	clinical testing	This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 180229). This premature translational stop signal has been observed in individual(s) with KAT6A-related conditions (PMID: 25728775, 32041641). In at least one individual the variant was observed to be de novo. This sequence change creates a premature translational stop signal (p.Arg1129*) in the KAT6A gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 876 amino acid(s) of the KAT6A protein.
Revvity Omics, Revvity	RCV000167546	SCV003820852	pathogenic	Autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome	2022-03-14	criteria provided, single submitter	clinical testing
Duke University Health System Sequencing Clinic, Duke University Health System	RCV000167546	SCV003918910	pathogenic	Autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome	2023-04-20	criteria provided, single submitter	research
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV001091600	SCV004026464	pathogenic	not provided	2022-04-06	criteria provided, single submitter	clinical testing	PVS1, PM2_SUP, PS3
Daryl Scott Lab, Baylor College of Medicine	RCV000167546	SCV004102699	pathogenic	Autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome	2023-11-10	criteria provided, single submitter	clinical testing
DECIPHERD-UDD, Universidad del Desarrollo	RCV000167546	SCV004171018	pathogenic	Autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome	2023-07-01	criteria provided, single submitter	research
UCLA Clinical Genomics Center, UCLA	RCV000170450	SCV000196747	pathogenic	KAT6A syndrome	2015-01-15	no assertion criteria provided	clinical testing
OMIM	RCV000167546	SCV000218421	pathogenic	Autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome	2015-03-05	no assertion criteria provided	literature only
Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille	RCV000170450	SCV001427760	pathogenic	KAT6A syndrome	2019-01-01	no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001091600	SCV001956450	pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001091600	SCV001968338	pathogenic	not provided		no assertion criteria provided	clinical testing