NM_020975.6(RET):c.2438G>A (p.Arg813Gln) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 6, 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:: RCV002458436.2

Allele description [Variation Report for NM_020975.6(RET):c.2438G>A (p.Arg813Gln)]

NM_020975.6(RET):c.2438G>A (p.Arg813Gln)

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.2438G>A (p.Arg813Gln)

HGVS:

NC_000010.11:g.43119576G>A
NG_007489.1:g.47508G>A
NM_000323.2:c.2438G>A
NM_001355216.2:c.1676G>A
NM_001406743.1:c.2438G>A
NM_001406744.1:c.2438G>A
NM_001406759.1:c.2438G>A
NM_001406760.1:c.2438G>A
NM_001406761.1:c.2309G>A
NM_001406762.1:c.2309G>A
NM_001406763.1:c.2303G>A
NM_001406764.1:c.2309G>A
NM_001406765.1:c.2303G>A
NM_001406766.1:c.2150G>A
NM_001406767.1:c.2150G>A
NM_001406768.1:c.2174G>A
NM_001406769.1:c.2042G>A
NM_001406770.1:c.2150G>A
NM_001406771.1:c.2000G>A
NM_001406772.1:c.2042G>A
NM_001406773.1:c.2000G>A
NM_001406774.1:c.1913G>A
NM_001406775.1:c.1712G>A
NM_001406776.1:c.1712G>A
NM_001406777.1:c.1712G>A
NM_001406778.1:c.1712G>A
NM_001406779.1:c.1541G>A
NM_001406780.1:c.1541G>A
NM_001406781.1:c.1541G>A
NM_001406782.1:c.1541G>A
NM_001406783.1:c.1412G>A
NM_001406784.1:c.1448G>A
NM_001406785.1:c.1421G>A
NM_001406786.1:c.1412G>A
NM_001406787.1:c.1406G>A
NM_001406788.1:c.1253G>A
NM_001406789.1:c.1253G>A
NM_001406790.1:c.1253G>A
NM_001406791.1:c.1133G>A
NM_001406792.1:c.989G>A
NM_001406793.1:c.989G>A
NM_001406794.1:c.989G>A
NM_020629.2:c.2438G>A
NM_020630.7:c.2438G>A
NM_020975.6:c.2438G>AMANE SELECT
NP_000314.1:p.Arg813Gln
NP_001342145.1:p.Arg559Gln
NP_001342145.1:p.Arg559Gln
NP_001393672.1:p.Arg813Gln
NP_001393673.1:p.Arg813Gln
NP_001393688.1:p.Arg813Gln
NP_001393689.1:p.Arg813Gln
NP_001393690.1:p.Arg770Gln
NP_001393691.1:p.Arg770Gln
NP_001393692.1:p.Arg768Gln
NP_001393693.1:p.Arg770Gln
NP_001393694.1:p.Arg768Gln
NP_001393695.1:p.Arg717Gln
NP_001393696.1:p.Arg717Gln
NP_001393697.1:p.Arg725Gln
NP_001393698.1:p.Arg681Gln
NP_001393699.1:p.Arg717Gln
NP_001393700.1:p.Arg667Gln
NP_001393701.1:p.Arg681Gln
NP_001393702.1:p.Arg667Gln
NP_001393703.1:p.Arg638Gln
NP_001393704.1:p.Arg571Gln
NP_001393705.1:p.Arg571Gln
NP_001393706.1:p.Arg571Gln
NP_001393707.1:p.Arg571Gln
NP_001393708.1:p.Arg514Gln
NP_001393709.1:p.Arg514Gln
NP_001393710.1:p.Arg514Gln
NP_001393711.1:p.Arg514Gln
NP_001393712.1:p.Arg471Gln
NP_001393713.1:p.Arg483Gln
NP_001393714.1:p.Arg474Gln
NP_001393715.1:p.Arg471Gln
NP_001393716.1:p.Arg469Gln
NP_001393717.1:p.Arg418Gln
NP_001393718.1:p.Arg418Gln
NP_001393719.1:p.Arg418Gln
NP_001393720.1:p.Arg378Gln
NP_001393721.1:p.Arg330Gln
NP_001393722.1:p.Arg330Gln
NP_001393723.1:p.Arg330Gln
NP_065680.1:p.Arg813Gln
NP_065681.1:p.Arg813Gln
NP_065681.1:p.Arg813Gln
NP_065681.1:p.Arg813Gln
NP_066124.1:p.Arg813Gln
NP_066124.1:p.Arg813Gln
LRG_518t1:c.2438G>A
LRG_518t2:c.2438G>A
LRG_518:g.47508G>A
LRG_518p1:p.Arg813Gln
LRG_518p2:p.Arg813Gln
NC_000010.10:g.43615024G>A
NM_001355216.1:c.1676G>A
NM_020630.4:c.2438G>A
NM_020630.6:c.2438G>A
NM_020975.4:c.2438G>A

Protein change:

R330Q

Links:

dbSNP: rs1318733775

NCBI 1000 Genomes Browser:

rs1318733775

Molecular consequence:

NM_000323.2:c.2438G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001355216.2:c.1676G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406743.1:c.2438G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406744.1:c.2438G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406759.1:c.2438G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406760.1:c.2438G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406761.1:c.2309G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406762.1:c.2309G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406763.1:c.2303G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406764.1:c.2309G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406765.1:c.2303G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406766.1:c.2150G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406767.1:c.2150G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406768.1:c.2174G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406769.1:c.2042G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406770.1:c.2150G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406771.1:c.2000G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406772.1:c.2042G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406773.1:c.2000G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406774.1:c.1913G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406775.1:c.1712G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406776.1:c.1712G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406777.1:c.1712G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406778.1:c.1712G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406779.1:c.1541G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406780.1:c.1541G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406781.1:c.1541G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406782.1:c.1541G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406783.1:c.1412G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406784.1:c.1448G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406785.1:c.1421G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406786.1:c.1412G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406787.1:c.1406G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406788.1:c.1253G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406789.1:c.1253G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406790.1:c.1253G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406791.1:c.1133G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406792.1:c.989G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406793.1:c.989G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406794.1:c.989G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_020629.2:c.2438G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_020630.7:c.2438G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_020975.6:c.2438G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

Recent activity

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eukaryotic translation initiation factor 4 gamma 3 isoform X23 [Mustela putorius...
eukaryotic translation initiation factor 4 gamma 3 isoform X23 [Mustela putorius furo]
gi|2130921316|ref|XP_044919842.1|

Protein
PREDICTED: Mustela putorius furo eukaryotic translation initiation factor 4 gamm...
PREDICTED: Mustela putorius furo eukaryotic translation initiation factor 4 gamma 3 (EIF4G3), transcript variant X5, mRNA
gi|2130921250|ref|XM_045063889.1|

Nucleotide
eukaryotic translation initiation factor 4 gamma 3 isoform X11 [Mustela putorius...
eukaryotic translation initiation factor 4 gamma 3 isoform X11 [Mustela putorius furo]
gi|2130921275|ref|XP_044919830.1|

Protein
eukaryotic translation initiation factor 4 gamma 3 isoform X8 [Mustela putorius ...
eukaryotic translation initiation factor 4 gamma 3 isoform X8 [Mustela putorius furo]
gi|2130921263|ref|XP_044919827.1|

Protein
eukaryotic translation initiation factor 4 gamma 3 isoform X17 [Mustela putorius...
eukaryotic translation initiation factor 4 gamma 3 isoform X17 [Mustela putorius furo]
gi|2130921293|ref|XP_044919836.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002737560	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Jul 6, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 10090908, 22729463, 22837065 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002737560

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Jul 6, 2021)

germline

clinical testing

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

Citation Link

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

Double heterozygosity for a RET substitution interfering with splicing and an EDNRB missense mutation in Hirschsprung disease.

Auricchio A, Griseri P, Carpentieri ML, Betsos N, Staiano A, Tozzi A, Priolo M, Thompson H, Bocciardi R, Romeo G, Ballabio A, Ceccherini I.

Am J Hum Genet. 1999 Apr;64(4):1216-21. No abstract available.

PubMed [citation]

PMID:: 10090908
PMCID:: PMC1377847

Traditional and targeted exome sequencing reveals common, rare and novel functional deleterious variants in RET-signaling complex in a cohort of living US patients with urinary tract malformations.

Chatterjee R, Ramos E, Hoffman M, VanWinkle J, Martin DR, Davis TK, Hoshi M, Hmiel SP, Beck A, Hruska K, Coplen D, Liapis H, Mitra R, Druley T, Austin P, Jain S.

Hum Genet. 2012 Nov;131(11):1725-38. doi: 10.1007/s00439-012-1181-3. Epub 2012 Jun 23.

PubMed [citation]

PMID:: 22729463
PMCID:: PMC3551468

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV002737560.2

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

Description

The p.R813Q variant (also known as c.2438G>A), located in coding exon 14 of the RET gene, results from a G to A substitution at nucleotide position 2438. The arginine at codon 813 is replaced by glutamine, an amino acid with highly similar properties. This alteration has been reported in multiple unrelated individuals with Hirschsprung disease (Auricchio A et al. Am J Hum Genet. 1999 Apr;64:1216-21; Hyndman BD et al. Hum Mutat. 2013 Jan;34:132-42). In in vitro functional assays, this alteration demonstrated impaired RET phosphorylation and colony formation (Hyndman BD et al. Hum Mutat. 2013 Jan;34:132-42; Chatterjee R et al. Hum Genet. 2012 Nov;131:1725-38). In silico splice site analysis predicts that this alteration will result in the creation or strengthening of a novel splice acceptor site. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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: Oct 8, 2024

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