NM_020975.6(RET):c.2452G>C (p.Glu818Gln) AND Multiple endocrine neoplasia, type 2

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 27, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV004017069.2

Allele description [Variation Report for NM_020975.6(RET):c.2452G>C (p.Glu818Gln)]

NM_020975.6(RET):c.2452G>C (p.Glu818Gln)

Gene:

RET:ret proto-oncogene [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q11.21

Genomic location:

Preferred name:

NM_020975.6(RET):c.2452G>C (p.Glu818Gln)

HGVS:

NC_000010.11:g.43119590G>C
NG_007489.1:g.47522G>C
NM_000323.2:c.2452G>C
NM_001355216.2:c.1690G>C
NM_001406743.1:c.2452G>C
NM_001406744.1:c.2452G>C
NM_001406759.1:c.2452G>C
NM_001406760.1:c.2452G>C
NM_001406761.1:c.2323G>C
NM_001406762.1:c.2323G>C
NM_001406763.1:c.2317G>C
NM_001406764.1:c.2323G>C
NM_001406765.1:c.2317G>C
NM_001406766.1:c.2164G>C
NM_001406767.1:c.2164G>C
NM_001406768.1:c.2188G>C
NM_001406769.1:c.2056G>C
NM_001406770.1:c.2164G>C
NM_001406771.1:c.2014G>C
NM_001406772.1:c.2056G>C
NM_001406773.1:c.2014G>C
NM_001406774.1:c.1927G>C
NM_001406775.1:c.1726G>C
NM_001406776.1:c.1726G>C
NM_001406777.1:c.1726G>C
NM_001406778.1:c.1726G>C
NM_001406779.1:c.1555G>C
NM_001406780.1:c.1555G>C
NM_001406781.1:c.1555G>C
NM_001406782.1:c.1555G>C
NM_001406783.1:c.1426G>C
NM_001406784.1:c.1462G>C
NM_001406785.1:c.1435G>C
NM_001406786.1:c.1426G>C
NM_001406787.1:c.1420G>C
NM_001406788.1:c.1267G>C
NM_001406789.1:c.1267G>C
NM_001406790.1:c.1267G>C
NM_001406791.1:c.1147G>C
NM_001406792.1:c.1003G>C
NM_001406793.1:c.1003G>C
NM_001406794.1:c.1003G>C
NM_020629.2:c.2452G>C
NM_020630.7:c.2452G>C
NM_020975.6:c.2452G>CMANE SELECT
NP_000314.1:p.Glu818Gln
NP_001342145.1:p.Glu564Gln
NP_001393672.1:p.Glu818Gln
NP_001393673.1:p.Glu818Gln
NP_001393688.1:p.Glu818Gln
NP_001393689.1:p.Glu818Gln
NP_001393690.1:p.Glu775Gln
NP_001393691.1:p.Glu775Gln
NP_001393692.1:p.Glu773Gln
NP_001393693.1:p.Glu775Gln
NP_001393694.1:p.Glu773Gln
NP_001393695.1:p.Glu722Gln
NP_001393696.1:p.Glu722Gln
NP_001393697.1:p.Glu730Gln
NP_001393698.1:p.Glu686Gln
NP_001393699.1:p.Glu722Gln
NP_001393700.1:p.Glu672Gln
NP_001393701.1:p.Glu686Gln
NP_001393702.1:p.Glu672Gln
NP_001393703.1:p.Glu643Gln
NP_001393704.1:p.Glu576Gln
NP_001393705.1:p.Glu576Gln
NP_001393706.1:p.Glu576Gln
NP_001393707.1:p.Glu576Gln
NP_001393708.1:p.Glu519Gln
NP_001393709.1:p.Glu519Gln
NP_001393710.1:p.Glu519Gln
NP_001393711.1:p.Glu519Gln
NP_001393712.1:p.Glu476Gln
NP_001393713.1:p.Glu488Gln
NP_001393714.1:p.Glu479Gln
NP_001393715.1:p.Glu476Gln
NP_001393716.1:p.Glu474Gln
NP_001393717.1:p.Glu423Gln
NP_001393718.1:p.Glu423Gln
NP_001393719.1:p.Glu423Gln
NP_001393720.1:p.Glu383Gln
NP_001393721.1:p.Glu335Gln
NP_001393722.1:p.Glu335Gln
NP_001393723.1:p.Glu335Gln
NP_065680.1:p.Glu818Gln
NP_065681.1:p.Glu818Gln
NP_065681.1:p.Glu818Gln
NP_066124.1:p.Glu818Gln
NP_066124.1:p.Glu818Gln
LRG_518t1:c.2452G>C
LRG_518t2:c.2452G>C
LRG_518:g.47522G>C
LRG_518p1:p.Glu818Gln
LRG_518p2:p.Glu818Gln
NC_000010.10:g.43615038G>C
NM_020630.4:c.2452G>C
NM_020975.4:c.2452G>C

Protein change:

E335Q

Molecular consequence:

NM_000323.2:c.2452G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001355216.2:c.1690G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406743.1:c.2452G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406744.1:c.2452G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406759.1:c.2452G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406760.1:c.2452G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406761.1:c.2323G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406762.1:c.2323G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406763.1:c.2317G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406764.1:c.2323G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406765.1:c.2317G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406766.1:c.2164G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406767.1:c.2164G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406768.1:c.2188G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406769.1:c.2056G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406770.1:c.2164G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406771.1:c.2014G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406772.1:c.2056G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406773.1:c.2014G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406774.1:c.1927G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406775.1:c.1726G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406776.1:c.1726G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406777.1:c.1726G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406778.1:c.1726G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406779.1:c.1555G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406780.1:c.1555G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406781.1:c.1555G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406782.1:c.1555G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406783.1:c.1426G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406784.1:c.1462G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406785.1:c.1435G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406786.1:c.1426G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406787.1:c.1420G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406788.1:c.1267G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406789.1:c.1267G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406790.1:c.1267G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406791.1:c.1147G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406792.1:c.1003G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406793.1:c.1003G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406794.1:c.1003G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_020629.2:c.2452G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_020630.7:c.2452G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_020975.6:c.2452G>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Multiple endocrine neoplasia, type 2 (MEN2)
Identifiers:: MONDO: MONDO:0019003; MedGen: C4048306

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Nectin1 nectin cell adhesion molecule 1 [Mus musculus]
Nectin1 nectin cell adhesion molecule 1 [Mus musculus]
Gene ID:58235

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BioAssay by Target (List) for Gene (Select 5818) (0)
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RefSeq Protein Links for Gene (Select 5818) (3)
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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004838672	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain Significance (Apr 27, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004838672

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain Significance
(Apr 27, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	1	not provided	not provided	108544	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From All of Us Research Program, National Institutes of Health, SCV004838672.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (1)

Description

This missense variant replaces glutamic acid with glutamine at codon 818 of the RET protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	108544	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Jun 2, 2024

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