ClinVar Miner

Submissions for variant NM_020975.6(RET):c.2944C>T (p.Arg982Cys) (rs17158558)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 22
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000082055 SCV000113994 benign not specified 2014-10-23 criteria provided, single submitter clinical testing
Invitae RCV001080524 SCV000153846 benign Multiple endocrine neoplasia, type 2 2019-12-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000162949 SCV000213436 benign Hereditary cancer-predisposing syndrome 2014-11-24 criteria provided, single submitter clinical testing
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.
Division of Genomic Diagnostics,The 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, Partners HealthCare 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).
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000238890 SCV000297299 benign Familial medullary thyroid carcinoma 2015-09-24 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000082055 SCV000313724 benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,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 Clinical Services Laboratory,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 Clinical Services Laboratory,Illumina RCV000014965 SCV000362378 likely benign Hirschsprung disease 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 Clinical Services Laboratory,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 Inc RCV000034774 SCV000842760 benign not provided 2017-12-21 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America 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.
OMIM RCV000014965 SCV000035221 risk factor Hirschsprung disease 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 Hirschsprung disease 2013-01-01 no assertion criteria provided research

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.