Submissions for variant NM_175914.5(HNF4A):c.427-4G>A

gnomAD frequency: 0.00021  dbSNP: rs146751799

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Athena Diagnostics	RCV000518191	SCV000613655	benign	not specified	2016-11-14	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000901336	SCV001045702	benign	not provided	2023-10-17	criteria provided, single submitter	clinical testing
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV001258240	SCV001435152	likely benign	Type 2 diabetes mellitus		criteria provided, single submitter	research	The heterozygous c.427-4G>A variant in HNF4A has been identified in 3 Philippino siblings from 1 family with maturity onset diabetes of the young (PMID: 15281001), but has also been identified in >1% of South Asian chromosomes and 4 homozygotes by ExAC (http://gnomad.broadinstitute.org/). Computational prediction tools suggest that this variant may impact splicing, though this information is not predictive enough to determine pathogenicity. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely benign for autosomal dominant diabetes mellitus type 2.
Genetic Services Laboratory, University of Chicago	RCV000518191	SCV002066212	benign	not specified	2019-05-02	criteria provided, single submitter	clinical testing
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV002226713	SCV002505493	uncertain significance	Maturity onset diabetes mellitus in young		criteria provided, single submitter	research	This mutation is associated with poor insulin secretion in response to hyperglycemia. Associated with MODY1. Patients initially respond well to sulfonylureas but eventually become insulin dependent. However, no sufficient evidence is found to ascertain the role of rs146751799 variant in Diabetes Mellitus yet.
Ambry Genetics	RCV002226713	SCV002631740	benign	Maturity onset diabetes mellitus in young	2021-04-27	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000518191	SCV002034108	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000901336	SCV002035422	likely benign	not provided		no assertion criteria provided	clinical testing