Submissions for variant NM_020975.6(RET):c.2284+4C>T

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002589952	SCV002949676	uncertain significance	Multiple endocrine neoplasia, type 2	2022-02-25	criteria provided, single submitter	clinical testing	This sequence change falls in intron 12 of the RET gene. It does not directly change the encoded amino acid sequence of the RET protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RET-related conditions. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
All of Us Research Program, National Institutes of Health	RCV002589952	SCV004825286	uncertain significance	Multiple endocrine neoplasia, type 2	2023-08-15	criteria provided, single submitter	clinical testing	This variant causes a C to T nucleotide substitution at the +4 position of intron 12 of the RET gene. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with RET-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Ambry Genetics	RCV004946018	SCV005490969	uncertain significance	Hereditary cancer-predisposing syndrome	2024-11-25	criteria provided, single submitter	clinical testing	The c.2284+4C>T intronic variant results from a C to T substitution 4 nucleotides after coding exon 12 in the RET gene. This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. Based on the available evidence, the clinical significance of this variant remains unclear.