ClinVar Miner

Submissions for variant NM_020975.6(RET):c.2944C>T (p.Arg982Cys)

gnomAD frequency: 0.01567  dbSNP: rs17158558
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 36
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000082055 SCV000113994 benign not specified 2014-10-23 criteria provided, single submitter clinical testing
Invitae RCV001080524 SCV000153846 benign Multiple endocrine neoplasia, type 2 2024-02-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV000162949 SCV000213436 benign Hereditary cancer-predisposing syndrome 2014-11-24 criteria provided, single submitter clinical testing This alteration is classified as 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 RCV000082055 SCV000234928 benign not specified 2016-09-23 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.
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia RCV000202663 SCV000258172 benign Multiple endocrine neoplasia 2015-04-17 criteria provided, single submitter clinical testing
Vantari Genetics RCV000162949 SCV000267090 benign Hereditary cancer-predisposing syndrome 2016-02-04 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000082055 SCV000269746 benign not specified 2015-12-09 criteria provided, single submitter clinical testing p.Arg982Cys in exon 18 of RET: This variant is not expected to have clinical sig nificance because it is not located within the splice consensus sequence. It has been identified in 4% (666/16512) of South Asian chromosomes by the Exome Aggre gation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs17158558).
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia RCV000238890 SCV000297299 benign Familial medullary thyroid carcinoma 2015-09-24 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV000082055 SCV000313724 benign not specified criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000202663 SCV000362376 likely benign Multiple endocrine neoplasia 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina RCV000354936 SCV000362377 likely benign Renal hypodysplasia/aplasia 1 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina RCV000014965 SCV000362378 likely benign Hirschsprung disease, susceptibility to, 1 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina RCV000320112 SCV000362379 likely benign Pheochromocytoma 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Counsyl RCV000410308 SCV000489799 benign Multiple endocrine neoplasia type 2B 2016-04-05 criteria provided, single submitter clinical testing
Counsyl RCV000411820 SCV000489800 benign Multiple endocrine neoplasia type 2A 2016-04-05 criteria provided, single submitter clinical testing
Center for Human Genetics, Inc, Center for Human Genetics, Inc RCV000411820 SCV000782261 uncertain significance Multiple endocrine neoplasia type 2A 2016-11-01 criteria provided, single submitter clinical testing
Athena Diagnostics RCV000034774 SCV000842760 benign not provided 2017-12-21 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000082055 SCV001363345 benign not specified 2019-12-23 criteria provided, single submitter clinical testing Variant summary: RET c.2944C>T (p.Arg982Cys) results in a non-conservative amino acid change located in the serine-threonine/tyrosine-protein kinase, catalytic domain (IPR001245) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.019 in 251460 control chromosomes in the gnomAD database, including 78 homozygotes. The observed variant frequency is approximately 1299 fold of the estimated maximal expected allele frequency for a pathogenic variant in RET causing Multiple Endocrine Neoplasia Type 2/Hirschsprung Disease phenotype (1.5e-05), strongly suggesting that the variant is benign. c.2944C>T has been reported in the early literature predating large control datasets in individuals reportedly affected with Multiple Endocrine Neoplasia Type 2/Hirschsprung Disease. These report(s) do not provide unequivocal conclusions about association of the variant with Multiple Endocrine Neoplasia Type 2/Hirschsprung Disease with no evidence supporting a damaging outcome in subsequent literature relating to this specific variant. At-least two co-occurrences with other pathogenic variant(s) have been reported (RET c.1852T>C, p.Cys618Arg; RET c.2410G>A, p.Val804Met), providing supporting evidence for a benign role (Mulligan_1994, and Lesueur_2005). At least one publication reports experimental evidence evaluating an impact on protein function. These results showed no damaging effect of this variant Pasini_1995. Nine clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (benign, n=7, likely benign, n=1, VUS, n=1). Based on the evidence outlined above, the variant was classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000034774 SCV002048343 benign not provided 2023-10-27 criteria provided, single submitter clinical testing
Department of Human Genetics, Hannover Medical School RCV001822995 SCV002072583 likely benign Breast-ovarian cancer, familial, susceptibility to, 1 2022-02-01 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000034774 SCV002497027 benign not provided 2024-04-01 criteria provided, single submitter clinical testing RET: BP4, BS1, BS2
Sema4, Sema4 RCV000162949 SCV002529995 benign Hereditary cancer-predisposing syndrome 2020-10-15 criteria provided, single submitter curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV000082055 SCV002550393 benign not specified 2023-08-15 criteria provided, single submitter clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center RCV000410308 SCV004017339 benign Multiple endocrine neoplasia type 2B 2023-07-07 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV001080524 SCV004357254 benign Multiple endocrine neoplasia, type 2 2022-06-09 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV001080524 SCV004838703 benign Multiple endocrine neoplasia, type 2 2024-02-05 criteria provided, single submitter clinical testing
OMIM RCV000014965 SCV000035221 risk factor Hirschsprung disease, susceptibility to, 1 1998-08-01 no assertion criteria provided literature only
Biesecker Lab/Clinical Genomics Section, National Institutes of Health RCV000034774 SCV000043479 no known pathogenicity not provided 2012-07-13 no assertion criteria provided research Converted during submission to Benign.
ITMI RCV000082055 SCV000086193 not provided not specified 2013-09-19 no assertion provided reference population
Human Genomics Unit, Institute for molecular medicine Finland (FIMM) RCV000736279 SCV000864577 uncertain significance Aganglionic megacolon 2013-01-01 no assertion criteria provided research
Center of Medical Genetics and Primary Health Care RCV001269493 SCV001449149 benign Malignant tumor of breast no assertion criteria provided clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000082055 SCV001742225 benign not specified no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000082055 SCV001807964 benign not specified no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000082055 SCV001926276 benign not specified no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000082055 SCV001952506 benign not specified no assertion criteria provided clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000034774 SCV002036341 likely benign not provided no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.