Submissions for variant NM_020975.6(RET):c.-2C>A

gnomAD frequency: 0.00049  dbSNP: rs876657980

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000221356	SCV000272367	uncertain significance	not specified	2016-01-06	criteria provided, single submitter	clinical testing	The c.-2C>A variant in RET has not been previously reported in individuals with pulmonary disease and data from large population studies is insufficient to asse ss the frequency of this variant. Computational prediction tools and conservatio n analysis are limited or unavailable for this variant. This variant is located in the 5' UTR and is part of the translation initiation (Kozak) sequence, but it s effect on translation is unknown. In summary, the clinical significance of the c.-2C>A variant is uncertain.
Ambry Genetics	RCV000572702	SCV000674788	likely benign	Hereditary cancer-predisposing syndrome	2022-05-06	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.
GeneDx	RCV001580474	SCV001817597	uncertain significance	not provided	2019-08-06	criteria provided, single submitter	clinical testing	Nucleotide substitution 2 base pairs upstream of the ATG translational start site in the 5' untranslated region (UTR); Nucleotide substitution has no predicted effect on splicing and is not conserved across species; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics	RCV002503860	SCV002815893	uncertain significance	Hirschsprung disease, susceptibility to, 1; Multiple endocrine neoplasia type 2B; Pheochromocytoma; Familial medullary thyroid carcinoma; Multiple endocrine neoplasia type 2A	2022-04-27	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004532763	SCV004728507	likely benign	RET-related disorder	2023-09-18	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).