NM_020975.6(RET):c.318G>A (p.Trp106Ter) AND Multiple endocrine neoplasia, type 2

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 13, 2021
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:: RCV001381565.6

Allele description [Variation Report for NM_020975.6(RET):c.318G>A (p.Trp106Ter)]

NM_020975.6(RET):c.318G>A (p.Trp106Ter)

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.318G>A (p.Trp106Ter)

HGVS:

NC_000010.11:g.43100703G>A
NG_007489.1:g.28635G>A
NM_000323.2:c.318G>A
NM_001406743.1:c.318G>A
NM_001406744.1:c.318G>A
NM_001406759.1:c.318G>A
NM_001406760.1:c.318G>A
NM_001406761.1:c.318G>A
NM_001406762.1:c.318G>A
NM_001406763.1:c.318G>A
NM_001406764.1:c.318G>A
NM_001406765.1:c.318G>A
NM_001406766.1:c.318G>A
NM_001406767.1:c.318G>A
NM_001406768.1:c.318G>A
NM_001406769.1:c.318G>A
NM_001406770.1:c.318G>A
NM_001406771.1:c.318G>A
NM_001406772.1:c.318G>A
NM_001406773.1:c.318G>A
NM_001406774.1:c.318G>A
NM_001406775.1:c.318G>A
NM_001406776.1:c.318G>A
NM_001406777.1:c.318G>A
NM_001406778.1:c.318G>A
NM_001406779.1:c.318G>A
NM_001406780.1:c.318G>A
NM_001406781.1:c.318G>A
NM_001406782.1:c.318G>A
NM_001406783.1:c.318G>A
NM_001406785.1:c.318G>A
NM_001406786.1:c.318G>A
NM_001406787.1:c.318G>A
NM_001406788.1:c.318G>A
NM_001406789.1:c.318G>A
NM_001406790.1:c.318G>A
NM_001406791.1:c.318G>A
NM_020629.2:c.318G>A
NM_020630.7:c.318G>A
NM_020975.6:c.318G>AMANE SELECT
NP_000314.1:p.Trp106Ter
NP_001393672.1:p.Trp106Ter
NP_001393673.1:p.Trp106Ter
NP_001393688.1:p.Trp106Ter
NP_001393689.1:p.Trp106Ter
NP_001393690.1:p.Trp106Ter
NP_001393691.1:p.Trp106Ter
NP_001393692.1:p.Trp106Ter
NP_001393693.1:p.Trp106Ter
NP_001393694.1:p.Trp106Ter
NP_001393695.1:p.Trp106Ter
NP_001393696.1:p.Trp106Ter
NP_001393697.1:p.Trp106Ter
NP_001393698.1:p.Trp106Ter
NP_001393699.1:p.Trp106Ter
NP_001393700.1:p.Trp106Ter
NP_001393701.1:p.Trp106Ter
NP_001393702.1:p.Trp106Ter
NP_001393703.1:p.Trp106Ter
NP_001393704.1:p.Trp106Ter
NP_001393705.1:p.Trp106Ter
NP_001393706.1:p.Trp106Ter
NP_001393707.1:p.Trp106Ter
NP_001393708.1:p.Trp106Ter
NP_001393709.1:p.Trp106Ter
NP_001393710.1:p.Trp106Ter
NP_001393711.1:p.Trp106Ter
NP_001393712.1:p.Trp106Ter
NP_001393714.1:p.Trp106Ter
NP_001393715.1:p.Trp106Ter
NP_001393716.1:p.Trp106Ter
NP_001393717.1:p.Trp106Ter
NP_001393718.1:p.Trp106Ter
NP_001393719.1:p.Trp106Ter
NP_001393720.1:p.Trp106Ter
NP_065680.1:p.Trp106Ter
NP_065681.1:p.Trp106Ter
NP_065681.1:p.Trp106Ter
NP_065681.1:p.Trp106Ter
NP_066124.1:p.Trp106Ter
NP_066124.1:p.Trp106Ter
LRG_518t1:c.318G>A
LRG_518t2:c.318G>A
LRG_518:g.28635G>A
LRG_518p1:p.Trp106Ter
LRG_518p2:p.Trp106Ter
NC_000010.10:g.43596151G>A
NM_020630.4:c.318G>A
NM_020630.6:c.318G>A
NM_020975.4:c.318G>A

Protein change:

W106*

Links:

dbSNP: rs2132664999

NCBI 1000 Genomes Browser:

rs2132664999

Molecular consequence:

NM_000323.2:c.318G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406743.1:c.318G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406744.1:c.318G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406759.1:c.318G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406760.1:c.318G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406761.1:c.318G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406762.1:c.318G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406763.1:c.318G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406764.1:c.318G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406765.1:c.318G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406766.1:c.318G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406767.1:c.318G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406768.1:c.318G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406769.1:c.318G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406770.1:c.318G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406771.1:c.318G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406772.1:c.318G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406773.1:c.318G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406774.1:c.318G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406775.1:c.318G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406776.1:c.318G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406777.1:c.318G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406778.1:c.318G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406779.1:c.318G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406780.1:c.318G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406781.1:c.318G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406782.1:c.318G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406783.1:c.318G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406785.1:c.318G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406786.1:c.318G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406787.1:c.318G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406788.1:c.318G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406789.1:c.318G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406790.1:c.318G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001406791.1:c.318G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_020629.2:c.318G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_020630.7:c.318G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_020975.6:c.318G>A - nonsense - [Sequence Ontology: SO:0001587]

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
SCV001580005	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 13, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 22174939, 22648184, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001580005

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 13, 2021)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

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

RET mutational spectrum in Hirschsprung disease: evaluation of 601 Chinese patients.

So MT, Leon TY, Cheng G, Tang CS, Miao XP, Cornes BK, Diem NN, Cui L, Ngan ES, Lui VC, Wu XZ, Wang B, Wang H, Yuan ZW, Huang LM, Li L, Xia H, Zhu D, Liu J, Nguyen TL, Chan IH, Chung PH, et al.

PLoS One. 2011;6(12):e28986. doi: 10.1371/journal.pone.0028986. Epub 2011 Dec 9.

PubMed [citation]

PMID:: 22174939
PMCID:: PMC3235168

Hirschsprung's disease and variants in genes that regulate enteric neural crest cell proliferation, migration and differentiation.

Carter TC, Kay DM, Browne ML, Liu A, Romitti PA, Kuehn D, Conley MR, Caggana M, Druschel CM, Brody LC, Mills JL.

J Hum Genet. 2012 Aug;57(8):485-93. doi: 10.1038/jhg.2012.54. Epub 2012 May 31.

PubMed [citation]

PMID:: 22648184
PMCID:: PMC3503526

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001580005.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with Hirschsprung disease (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Trp106*) in the RET gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RET are known to be pathogenic (PMID: 22174939, 22648184).

#	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

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