NM_020975.6(RET):c.182A>C (p.Glu61Ala) AND Multiple endocrine neoplasia, type 2

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 6, 2022
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:: RCV002532885.3

Allele description [Variation Report for NM_020975.6(RET):c.182A>C (p.Glu61Ala)]

NM_020975.6(RET):c.182A>C (p.Glu61Ala)

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.182A>C (p.Glu61Ala)

HGVS:

NC_000010.11:g.43100567A>C
NG_007489.1:g.28499A>C
NM_000323.2:c.182A>C
NM_001406743.1:c.182A>C
NM_001406744.1:c.182A>C
NM_001406759.1:c.182A>C
NM_001406760.1:c.182A>C
NM_001406761.1:c.182A>C
NM_001406762.1:c.182A>C
NM_001406763.1:c.182A>C
NM_001406764.1:c.182A>C
NM_001406765.1:c.182A>C
NM_001406766.1:c.182A>C
NM_001406767.1:c.182A>C
NM_001406768.1:c.182A>C
NM_001406769.1:c.182A>C
NM_001406770.1:c.182A>C
NM_001406771.1:c.182A>C
NM_001406772.1:c.182A>C
NM_001406773.1:c.182A>C
NM_001406774.1:c.182A>C
NM_001406775.1:c.182A>C
NM_001406776.1:c.182A>C
NM_001406777.1:c.182A>C
NM_001406778.1:c.182A>C
NM_001406779.1:c.182A>C
NM_001406780.1:c.182A>C
NM_001406781.1:c.182A>C
NM_001406782.1:c.182A>C
NM_001406783.1:c.182A>C
NM_001406785.1:c.182A>C
NM_001406786.1:c.182A>C
NM_001406787.1:c.182A>C
NM_001406788.1:c.182A>C
NM_001406789.1:c.182A>C
NM_001406790.1:c.182A>C
NM_001406791.1:c.182A>C
NM_020629.2:c.182A>C
NM_020630.7:c.182A>C
NM_020975.6:c.182A>CMANE SELECT
NP_000314.1:p.Glu61Ala
NP_001393672.1:p.Glu61Ala
NP_001393673.1:p.Glu61Ala
NP_001393688.1:p.Glu61Ala
NP_001393689.1:p.Glu61Ala
NP_001393690.1:p.Glu61Ala
NP_001393691.1:p.Glu61Ala
NP_001393692.1:p.Glu61Ala
NP_001393693.1:p.Glu61Ala
NP_001393694.1:p.Glu61Ala
NP_001393695.1:p.Glu61Ala
NP_001393696.1:p.Glu61Ala
NP_001393697.1:p.Glu61Ala
NP_001393698.1:p.Glu61Ala
NP_001393699.1:p.Glu61Ala
NP_001393700.1:p.Glu61Ala
NP_001393701.1:p.Glu61Ala
NP_001393702.1:p.Glu61Ala
NP_001393703.1:p.Glu61Ala
NP_001393704.1:p.Glu61Ala
NP_001393705.1:p.Glu61Ala
NP_001393706.1:p.Glu61Ala
NP_001393707.1:p.Glu61Ala
NP_001393708.1:p.Glu61Ala
NP_001393709.1:p.Glu61Ala
NP_001393710.1:p.Glu61Ala
NP_001393711.1:p.Glu61Ala
NP_001393712.1:p.Glu61Ala
NP_001393714.1:p.Glu61Ala
NP_001393715.1:p.Glu61Ala
NP_001393716.1:p.Glu61Ala
NP_001393717.1:p.Glu61Ala
NP_001393718.1:p.Glu61Ala
NP_001393719.1:p.Glu61Ala
NP_001393720.1:p.Glu61Ala
NP_065680.1:p.Glu61Ala
NP_065681.1:p.Glu61Ala
NP_065681.1:p.Glu61Ala
NP_065681.1:p.Glu61Ala
NP_066124.1:p.Glu61Ala
NP_066124.1:p.Glu61Ala
LRG_518t1:c.182A>C
LRG_518t2:c.182A>C
LRG_518:g.28499A>C
LRG_518p1:p.Glu61Ala
LRG_518p2:p.Glu61Ala
NC_000010.10:g.43596015A>C
NM_020630.4:c.182A>C
NM_020630.6:c.182A>C
NM_020975.4:c.182A>C
NM_020975.5:c.182A>C

Protein change:

E61A

Links:

dbSNP: rs1564489398

NCBI 1000 Genomes Browser:

rs1564489398

Molecular consequence:

NM_000323.2:c.182A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406743.1:c.182A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406744.1:c.182A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406759.1:c.182A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406760.1:c.182A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406761.1:c.182A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406762.1:c.182A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406763.1:c.182A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406764.1:c.182A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406765.1:c.182A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406766.1:c.182A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406767.1:c.182A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406768.1:c.182A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406769.1:c.182A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406770.1:c.182A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406771.1:c.182A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406772.1:c.182A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406773.1:c.182A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406774.1:c.182A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406775.1:c.182A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406776.1:c.182A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406777.1:c.182A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406778.1:c.182A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406779.1:c.182A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406780.1:c.182A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406781.1:c.182A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406782.1:c.182A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406783.1:c.182A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406785.1:c.182A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406786.1:c.182A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406787.1:c.182A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406788.1:c.182A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406789.1:c.182A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406790.1:c.182A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406791.1:c.182A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_020629.2:c.182A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_020630.7:c.182A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_020975.6:c.182A>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003450943	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 6, 2022)	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

SCV003450943

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 6, 2022)

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	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003450943.2

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

Description

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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 584562). This variant has not been reported in the literature in individuals affected with RET-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 61 of the RET protein (p.Glu61Ala).

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

Last Updated: Sep 29, 2024

ClinVar

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