NM_020975.6(RET):c.299G>A (p.Ser100Asn) AND Multiple endocrine neoplasia, type 2

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 19, 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:: RCV001858384.5

Allele description [Variation Report for NM_020975.6(RET):c.299G>A (p.Ser100Asn)]

NM_020975.6(RET):c.299G>A (p.Ser100Asn)

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.299G>A (p.Ser100Asn)

HGVS:

NC_000010.11:g.43100684G>A
NG_007489.1:g.28616G>A
NM_000323.2:c.299G>A
NM_001406743.1:c.299G>A
NM_001406744.1:c.299G>A
NM_001406759.1:c.299G>A
NM_001406760.1:c.299G>A
NM_001406761.1:c.299G>A
NM_001406762.1:c.299G>A
NM_001406763.1:c.299G>A
NM_001406764.1:c.299G>A
NM_001406765.1:c.299G>A
NM_001406766.1:c.299G>A
NM_001406767.1:c.299G>A
NM_001406768.1:c.299G>A
NM_001406769.1:c.299G>A
NM_001406770.1:c.299G>A
NM_001406771.1:c.299G>A
NM_001406772.1:c.299G>A
NM_001406773.1:c.299G>A
NM_001406774.1:c.299G>A
NM_001406775.1:c.299G>A
NM_001406776.1:c.299G>A
NM_001406777.1:c.299G>A
NM_001406778.1:c.299G>A
NM_001406779.1:c.299G>A
NM_001406780.1:c.299G>A
NM_001406781.1:c.299G>A
NM_001406782.1:c.299G>A
NM_001406783.1:c.299G>A
NM_001406785.1:c.299G>A
NM_001406786.1:c.299G>A
NM_001406787.1:c.299G>A
NM_001406788.1:c.299G>A
NM_001406789.1:c.299G>A
NM_001406790.1:c.299G>A
NM_001406791.1:c.299G>A
NM_020629.2:c.299G>A
NM_020630.7:c.299G>A
NM_020975.6:c.299G>AMANE SELECT
NP_000314.1:p.Ser100Asn
NP_001393672.1:p.Ser100Asn
NP_001393673.1:p.Ser100Asn
NP_001393688.1:p.Ser100Asn
NP_001393689.1:p.Ser100Asn
NP_001393690.1:p.Ser100Asn
NP_001393691.1:p.Ser100Asn
NP_001393692.1:p.Ser100Asn
NP_001393693.1:p.Ser100Asn
NP_001393694.1:p.Ser100Asn
NP_001393695.1:p.Ser100Asn
NP_001393696.1:p.Ser100Asn
NP_001393697.1:p.Ser100Asn
NP_001393698.1:p.Ser100Asn
NP_001393699.1:p.Ser100Asn
NP_001393700.1:p.Ser100Asn
NP_001393701.1:p.Ser100Asn
NP_001393702.1:p.Ser100Asn
NP_001393703.1:p.Ser100Asn
NP_001393704.1:p.Ser100Asn
NP_001393705.1:p.Ser100Asn
NP_001393706.1:p.Ser100Asn
NP_001393707.1:p.Ser100Asn
NP_001393708.1:p.Ser100Asn
NP_001393709.1:p.Ser100Asn
NP_001393710.1:p.Ser100Asn
NP_001393711.1:p.Ser100Asn
NP_001393712.1:p.Ser100Asn
NP_001393714.1:p.Ser100Asn
NP_001393715.1:p.Ser100Asn
NP_001393716.1:p.Ser100Asn
NP_001393717.1:p.Ser100Asn
NP_001393718.1:p.Ser100Asn
NP_001393719.1:p.Ser100Asn
NP_001393720.1:p.Ser100Asn
NP_065680.1:p.Ser100Asn
NP_065681.1:p.Ser100Asn
NP_065681.1:p.Ser100Asn
NP_065681.1:p.Ser100Asn
NP_066124.1:p.Ser100Asn
NP_066124.1:p.Ser100Asn
LRG_518t1:c.299G>A
LRG_518t2:c.299G>A
LRG_518:g.28616G>A
LRG_518p1:p.Ser100Asn
LRG_518p2:p.Ser100Asn
NC_000010.10:g.43596132G>A
NM_020630.4:c.299G>A
NM_020630.6:c.299G>A
NM_020975.4:c.299G>A

Protein change:

S100N

Links:

dbSNP: rs1554817407

NCBI 1000 Genomes Browser:

rs1554817407

Molecular consequence:

NM_000323.2:c.299G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406743.1:c.299G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406744.1:c.299G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406759.1:c.299G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406760.1:c.299G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406761.1:c.299G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406762.1:c.299G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406763.1:c.299G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406764.1:c.299G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406765.1:c.299G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406766.1:c.299G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406767.1:c.299G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406768.1:c.299G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406769.1:c.299G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406770.1:c.299G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406771.1:c.299G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406772.1:c.299G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406773.1:c.299G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406774.1:c.299G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406775.1:c.299G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406776.1:c.299G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406777.1:c.299G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406778.1:c.299G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406779.1:c.299G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406780.1:c.299G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406781.1:c.299G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406782.1:c.299G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406783.1:c.299G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406785.1:c.299G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406786.1:c.299G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406787.1:c.299G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406788.1:c.299G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406789.1:c.299G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406790.1:c.299G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406791.1:c.299G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_020629.2:c.299G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_020630.7:c.299G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_020975.6:c.299G>A - 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
SCV002279472	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 19, 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

SCV002279472

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 19, 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	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, SCV002279472.3

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

Description

This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 100 of the RET protein (p.Ser100Asn). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RET-related conditions. ClinVar contains an entry for this variant (Variation ID: 486346). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.

#	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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