Submissions for variant NM_001122659.3(EDNRB):c.914G>A (p.Ser305Asn) (rs5352)

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine	RCV000222856	SCV000269066	benign	not specified	2015-01-13	criteria provided, single submitter	clinical testing	p.Ser395Asn in exon 5 of EDNRB: This variant is not expected to have clinical si gnificance because it has been identified in 1.4% (119/8600) of European America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS; dbSNP rs5352).
PreventionGenetics,PreventionGenetics	RCV000222856	SCV000302327	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV000018118	SCV000384810	uncertain significance	Hirschsprung disease 2	2018-03-06	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Laboratory of Human Genetics,Universidade de São Paulo	RCV000626404	SCV000678739	likely benign	Waardenburg syndrome type 2A	2017-03-01	criteria provided, single submitter	research
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics	RCV000222856	SCV000707740	benign	not specified	2017-05-10	criteria provided, single submitter	clinical testing
GeneDx	RCV000954472	SCV000727101	benign	not provided	2019-05-10	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 22995991, 26764160, 27535533, 10874640, 8852659, 21507037)
Center for Human Genetics, Inc,Center for Human Genetics, Inc	RCV000659497	SCV000781315	likely benign	Waardenburg syndrome type 4A	2016-11-01	criteria provided, single submitter	clinical testing
Invitae	RCV000954472	SCV001101107	benign	not provided	2020-11-10	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000954472	SCV001143835	benign	not provided	2018-12-29	criteria provided, single submitter	clinical testing
Broad Institute Rare Disease Group, Broad Institute	RCV001258252	SCV001435166	benign	Mitochondrial DNA depletion syndrome 12a (cardiomyopathic type), autosomal dominant		criteria provided, single submitter	research	The heterozygous p.Ser305Asn variant, sometimes called p.Ser205Asn or p.Ser295Asn, in EDNRB has been identified in at least 6 individuals with Hirschsprung disease, including 4 relatives from 1 family (PMID: 8852659, 10874640, 22995991). However, this variant does not segregate with disease (PMID: 10874640), and has been identified in >2% of European (Finnish) chromosomes and 5 homozygotes in ExAC (http://gnomad.broadinstitute.org/). In summary, this variant meets criteria to be classified as benign for Hirschsprung disease.
OMIM	RCV000018118	SCV000038397	risk factor	Hirschsprung disease 2	1999-04-01	no assertion criteria provided	literature only