NM_020975.6(RET):c.2611G>A (p.Val871Ile) AND Hereditary cancer-predisposing syndrome

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Dec 11, 2021
Review status:: criteria provided, conflicting classifications

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:: RCV000562304.15

Allele description [Variation Report for NM_020975.6(RET):c.2611G>A (p.Val871Ile)]

NM_020975.6(RET):c.2611G>A (p.Val871Ile)

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.2611G>A (p.Val871Ile)

HGVS:

NC_000010.11:g.43120084G>A
NG_007489.1:g.48016G>A
NM_000323.2:c.2611G>A
NM_001355216.2:c.1849G>A
NM_001406743.1:c.2611G>A
NM_001406744.1:c.2611G>A
NM_001406759.1:c.2611G>A
NM_001406760.1:c.2611G>A
NM_001406761.1:c.2482G>A
NM_001406762.1:c.2482G>A
NM_001406763.1:c.2476G>A
NM_001406764.1:c.2482G>A
NM_001406765.1:c.2476G>A
NM_001406766.1:c.2323G>A
NM_001406767.1:c.2323G>A
NM_001406768.1:c.2347G>A
NM_001406769.1:c.2215G>A
NM_001406770.1:c.2323G>A
NM_001406771.1:c.2173G>A
NM_001406772.1:c.2215G>A
NM_001406773.1:c.2173G>A
NM_001406774.1:c.2086G>A
NM_001406775.1:c.1885G>A
NM_001406776.1:c.1885G>A
NM_001406777.1:c.1885G>A
NM_001406778.1:c.1885G>A
NM_001406779.1:c.1714G>A
NM_001406780.1:c.1714G>A
NM_001406781.1:c.1714G>A
NM_001406782.1:c.1714G>A
NM_001406783.1:c.1585G>A
NM_001406784.1:c.1621G>A
NM_001406785.1:c.1594G>A
NM_001406786.1:c.1585G>A
NM_001406787.1:c.1579G>A
NM_001406788.1:c.1426G>A
NM_001406789.1:c.1426G>A
NM_001406790.1:c.1426G>A
NM_001406791.1:c.1306G>A
NM_001406792.1:c.1162G>A
NM_001406793.1:c.1162G>A
NM_001406794.1:c.1162G>A
NM_020629.2:c.2611G>A
NM_020630.7:c.2611G>A
NM_020975.6:c.2611G>AMANE SELECT
NP_000314.1:p.Val871Ile
NP_001342145.1:p.Val617Ile
NP_001342145.1:p.Val617Ile
NP_001393672.1:p.Val871Ile
NP_001393673.1:p.Val871Ile
NP_001393688.1:p.Val871Ile
NP_001393689.1:p.Val871Ile
NP_001393690.1:p.Val828Ile
NP_001393691.1:p.Val828Ile
NP_001393692.1:p.Val826Ile
NP_001393693.1:p.Val828Ile
NP_001393694.1:p.Val826Ile
NP_001393695.1:p.Val775Ile
NP_001393696.1:p.Val775Ile
NP_001393697.1:p.Val783Ile
NP_001393698.1:p.Val739Ile
NP_001393699.1:p.Val775Ile
NP_001393700.1:p.Val725Ile
NP_001393701.1:p.Val739Ile
NP_001393702.1:p.Val725Ile
NP_001393703.1:p.Val696Ile
NP_001393704.1:p.Val629Ile
NP_001393705.1:p.Val629Ile
NP_001393706.1:p.Val629Ile
NP_001393707.1:p.Val629Ile
NP_001393708.1:p.Val572Ile
NP_001393709.1:p.Val572Ile
NP_001393710.1:p.Val572Ile
NP_001393711.1:p.Val572Ile
NP_001393712.1:p.Val529Ile
NP_001393713.1:p.Val541Ile
NP_001393714.1:p.Val532Ile
NP_001393715.1:p.Val529Ile
NP_001393716.1:p.Val527Ile
NP_001393717.1:p.Val476Ile
NP_001393718.1:p.Val476Ile
NP_001393719.1:p.Val476Ile
NP_001393720.1:p.Val436Ile
NP_001393721.1:p.Val388Ile
NP_001393722.1:p.Val388Ile
NP_001393723.1:p.Val388Ile
NP_065680.1:p.Val871Ile
NP_065681.1:p.Val871Ile
NP_065681.1:p.Val871Ile
NP_065681.1:p.Val871Ile
NP_066124.1:p.Val871Ile
NP_066124.1:p.Val871Ile
NP_066124.1:p.Val871Ile
LRG_518t1:c.2611G>A
LRG_518t2:c.2611G>A
LRG_518:g.48016G>A
LRG_518p1:p.Val871Ile
LRG_518p2:p.Val871Ile
NC_000010.10:g.43615532G>A
NM_001355216.1:c.1849G>A
NM_020630.4:c.2611G>A
NM_020630.6:c.2611G>A
NM_020975.4:c.2611G>A

Protein change:

V388I

Links:

dbSNP: rs145170911

NCBI 1000 Genomes Browser:

rs145170911

Molecular consequence:

NM_000323.2:c.2611G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001355216.2:c.1849G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406743.1:c.2611G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406744.1:c.2611G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406759.1:c.2611G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406760.1:c.2611G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406761.1:c.2482G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406762.1:c.2482G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406763.1:c.2476G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406764.1:c.2482G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406765.1:c.2476G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406766.1:c.2323G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406767.1:c.2323G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406768.1:c.2347G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406769.1:c.2215G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406770.1:c.2323G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406771.1:c.2173G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406772.1:c.2215G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406773.1:c.2173G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406774.1:c.2086G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406775.1:c.1885G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406776.1:c.1885G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406777.1:c.1885G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406778.1:c.1885G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406779.1:c.1714G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406780.1:c.1714G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406781.1:c.1714G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406782.1:c.1714G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406783.1:c.1585G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406784.1:c.1621G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406785.1:c.1594G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406786.1:c.1585G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406787.1:c.1579G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406788.1:c.1426G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406789.1:c.1426G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406790.1:c.1426G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406791.1:c.1306G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406792.1:c.1162G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406793.1:c.1162G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406794.1:c.1162G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_020629.2:c.2611G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_020630.7:c.2611G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_020975.6:c.2611G>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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000664502	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Benign (Aug 27, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV002529985	Sema4, Sema4	criteria provided, single submitter (Sema4 Curation Guidelines)	Uncertain significance (Dec 11, 2021)	germline	curation	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000664502

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Benign
(Aug 27, 2021)

germline

clinical testing

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

Citation Link,

SCV002529985

Sema4, Sema4

criteria provided, single submitter

(Sema4 Curation Guidelines)

Uncertain significance
(Dec 11, 2021)

germline

curation

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

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, curation

Citations

PubMed

Twenty-Five Years Experience on RET Genetic Screening on Hereditary MTC: An Update on The Prevalence of Germline RET Mutations.

Elisei R, Tacito A, Ramone T, Ciampi R, Bottici V, Cappagli V, Viola D, Matrone A, Lorusso L, Valerio L, Giani C, Campopiano C, Prete A, Agate L, Molinaro E, Romei C.

Genes (Basel). 2019 Sep 10;10(9). doi:pii: E698. 10.3390/genes10090698.

PubMed [citation]

PMID:: 31510104
PMCID:: PMC6771015

Details of each submission

From Ambry Genetics, SCV000664502.5

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

Description

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

#	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

From Sema4, Sema4, SCV002529985.1

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

#	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 26, 2024

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