Submissions for variant NM_020975.6(RET):c.73+9277T>C

gnomAD frequency: 0.79636  dbSNP: rs2435357

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000611595	SCV000729738	benign	not specified	2017-12-06	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Center of Genomic medicine, Geneva, University Hospital of Geneva	RCV000627056	SCV000747764	risk factor	Aganglionic megacolon	2017-11-20	criteria provided, single submitter	clinical testing	This variant was identified in a patient with Hirschsprung disease and a positive familial history. The patient harbours also a variant in the SEMA3D gene, which is a VUS for this disease.
Invitae	RCV001515285	SCV001723323	benign	Multiple endocrine neoplasia, type 2	2024-01-22	criteria provided, single submitter	clinical testing
OMIM	RCV000014980	SCV000035236	risk factor	Hirschsprung disease, susceptibility to, 1	2010-07-09	no assertion criteria provided	literature only
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics	RCV000014980	SCV001167343	risk factor	Hirschsprung disease, susceptibility to, 1	2020-02-19	no assertion criteria provided	clinical testing	A heterozygous variant c.73+9277T>C in intron 1 of the RET gene was detected. Presence of this allele has been identified to increase risk of Hirschprung disease by 5.7X compared to people who don't carry the variant (Virtanen et al. EJHG 2019). The allele frequency for the variant is 0.774 as given in gnomAD genomes. In summary, the variant meets our criteria to be classified as a risk factor for Hirschprung disease.