Submissions for variant NM_000245.4(MET):c.2584-7del

dbSNP: rs587780736

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001507223	SCV000166419	benign	Renal cell carcinoma	2024-02-01	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000723812	SCV000225560	uncertain significance	not provided	2014-10-28	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000123117	SCV000466453	likely benign	Papillary renal cell carcinoma type 1	2016-06-14	criteria provided, single submitter	clinical testing
GeneDx	RCV000174283	SCV000569535	likely benign	not specified	2017-11-02	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.
Genetic Services Laboratory, University of Chicago	RCV000174283	SCV002069846	likely benign	not specified	2021-08-19	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV002257476	SCV002532129	benign	Hereditary cancer-predisposing syndrome	2020-08-06	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000174283	SCV002550806	likely benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000174283	SCV002766140	benign	not specified	2022-11-03	criteria provided, single submitter	clinical testing	Variant summary: MET c.2638-7delC alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0016 in 239374 control chromosomes. The observed variant frequency is approximately 1050 fold of the estimated maximal expected allele frequency for a pathogenic variant in MET causing Papillary Renal Cell Carcinoma phenotype (1.5e-06), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.2638-7delC in individuals affected with Papillary Renal Cell Carcinoma and no experimental evidence demonstrating its impact on protein function have been reported. Six ClinVar submitters (evaluation after 2014) cite the variant as benign (n=2) and likely benign (n=4). Based on the evidence outlined above, the variant was classified as benign.