VCV000477349.54 - ClinVar

NM_020975.6(RET):c.2418C>T (p.Tyr806=)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Benign/Likely benign

12 out of 12 submissions contributed to this classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_020975.6(RET):c.2418C>T (p.Tyr806=)

Variation ID: 477349 Accession: VCV000477349.54

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 10q11.21 10: 43119556 (GRCh38) [ NCBI UCSC ] 10: 43615004 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Jan 1, 2018	Mar 7, 2026	Feb 2, 2026

HGVS

Nucleotide	Protein	Molecular consequence
NM_020975.6:c.2418C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_066124.1:p.Tyr806=	synonymous
NM_000323.2:c.2418C>T	NP_000314.1:p.Tyr806=	synonymous
NM_001355216.2:c.1656C>T	NP_001342145.1:p.Tyr552=	synonymous
NM_001406743.1:c.2418C>T	NP_001393672.1:p.Tyr806=	synonymous
NM_001406744.1:c.2418C>T	NP_001393673.1:p.Tyr806=	synonymous
NM_001406759.1:c.2418C>T	NP_001393688.1:p.Tyr806=	synonymous
NM_001406760.1:c.2418C>T	NP_001393689.1:p.Tyr806=	synonymous
NM_001406761.1:c.2289C>T	NP_001393690.1:p.Tyr763=	synonymous
NM_001406762.1:c.2289C>T	NP_001393691.1:p.Tyr763=	synonymous
NM_001406763.1:c.2283C>T	NP_001393692.1:p.Tyr761=	synonymous
NM_001406764.1:c.2289C>T	NP_001393693.1:p.Tyr763=	synonymous
NM_001406765.1:c.2283C>T	NP_001393694.1:p.Tyr761=	synonymous
NM_001406766.1:c.2130C>T	NP_001393695.1:p.Tyr710=	synonymous
NM_001406767.1:c.2130C>T	NP_001393696.1:p.Tyr710=	synonymous
NM_001406768.1:c.2154C>T	NP_001393697.1:p.Tyr718=	synonymous
NM_001406769.1:c.2022C>T	NP_001393698.1:p.Tyr674=	synonymous
NM_001406770.1:c.2130C>T	NP_001393699.1:p.Tyr710=	synonymous
NM_001406771.1:c.1980C>T	NP_001393700.1:p.Tyr660=	synonymous
NM_001406772.1:c.2022C>T	NP_001393701.1:p.Tyr674=	synonymous
NM_001406773.1:c.1980C>T	NP_001393702.1:p.Tyr660=	synonymous
NM_001406774.1:c.1893C>T	NP_001393703.1:p.Tyr631=	synonymous
NM_001406775.1:c.1692C>T	NP_001393704.1:p.Tyr564=	synonymous
NM_001406776.1:c.1692C>T	NP_001393705.1:p.Tyr564=	synonymous
NM_001406777.1:c.1692C>T	NP_001393706.1:p.Tyr564=	synonymous
NM_001406778.1:c.1692C>T	NP_001393707.1:p.Tyr564=	synonymous
NM_001406779.1:c.1521C>T	NP_001393708.1:p.Tyr507=	synonymous
NM_001406780.1:c.1521C>T	NP_001393709.1:p.Tyr507=	synonymous
NM_001406781.1:c.1521C>T	NP_001393710.1:p.Tyr507=	synonymous
NM_001406782.1:c.1521C>T	NP_001393711.1:p.Tyr507=	synonymous
NM_001406783.1:c.1392C>T	NP_001393712.1:p.Tyr464=	synonymous
NM_001406784.1:c.1428C>T	NP_001393713.1:p.Tyr476=	synonymous
NM_001406785.1:c.1401C>T	NP_001393714.1:p.Tyr467=	synonymous
NM_001406786.1:c.1392C>T	NP_001393715.1:p.Tyr464=	synonymous
NM_001406787.1:c.1386C>T	NP_001393716.1:p.Tyr462=	synonymous
NM_001406788.1:c.1233C>T	NP_001393717.1:p.Tyr411=	synonymous
NM_001406789.1:c.1233C>T	NP_001393718.1:p.Tyr411=	synonymous
NM_001406790.1:c.1233C>T	NP_001393719.1:p.Tyr411=	synonymous
NM_001406791.1:c.1113C>T	NP_001393720.1:p.Tyr371=	synonymous
NM_001406792.1:c.969C>T	NP_001393721.1:p.Tyr323=	synonymous
NM_001406793.1:c.969C>T	NP_001393722.1:p.Tyr323=	synonymous
NM_001406794.1:c.969C>T	NP_001393723.1:p.Tyr323=	synonymous
NM_020629.2:c.2418C>T	NP_065680.1:p.Tyr806=	synonymous
NM_020630.7:c.2418C>T	NP_065681.1:p.Tyr806=	synonymous
NC_000010.11:g.43119556C>T
NC_000010.10:g.43615004C>T
NG_007489.1:g.47488C>T
LRG_518:g.47488C>T
LRG_518t1:c.2418C>T	LRG_518p1:p.Tyr806=
LRG_518t2:c.2418C>T	LRG_518p2:p.Tyr806=

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000010.11:43119555:C:T

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.00020 (T)

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD) 0.00005

Trans-Omics for Precision Medicine (TOPMed) 0.00005

The Genome Aggregation Database (gnomAD), exomes 0.00008

Exome Aggregation Consortium (ExAC) 0.00014

The Genome Aggregation Database (gnomAD), exomes 0.00014

1000 Genomes Project 30x 0.00016

1000 Genomes Project 0.00020

Links

ClinGen: CA039132 dbSNP: rs553418132 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
RET		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	3848	3967

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
not provided	Likely benign (1)	criteria provided, single submitter	Aug 1, 2023	RCV001815346.32
Multiple endocrine neoplasia	Benign (1)	criteria provided, single submitter	Feb 12, 2018	RCV001102859.5
Renal hypodysplasia/aplasia 1	Likely benign (1)	criteria provided, single submitter	Feb 12, 2018	RCV001104777.5
Hirschsprung disease, susceptibility to, 1	Likely benign (1)	criteria provided, single submitter	Feb 12, 2018	RCV001104778.5
Pheochromocytoma	Benign (2)	criteria provided, multiple submitters, no conflicts	Feb 1, 2025	RCV001102860.6
Hereditary cancer-predisposing syndrome	Likely benign (1)	criteria provided, single submitter	Feb 5, 2016	RCV000568889.4
Multiple endocrine neoplasia, type 2	Likely benign (2)	criteria provided, multiple submitters, no conflicts	Feb 2, 2026	RCV000551962.15
not specified	Likely benign (2)	criteria provided, multiple submitters, no conflicts	Feb 16, 2025	RCV001821653.5
Multiple endocrine neoplasia type 2A	Benign (1)	criteria provided, single submitter	Feb 27, 2025	RCV005426168.1

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	Expand all rows Collapse all rows Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Likely benign (Dec 03, 2020) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	not specified	Genetic Services Laboratory, University of Chicago Accession: SCV002068678.1 First in ClinVar: Jan 29, 2022 Last updated: Jan 29, 2022	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: no Observation 1 Collection method: clinical testing Allele origin: germline Affected status: no

Likely benign (Feb 02, 2026) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Multiple endocrine neoplasia, type 2	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000658450.10 First in ClinVar: Dec 26, 2017 Last updated: Mar 07, 2026	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Likely benign (Aug 01, 2023) C Contributing to aggregate classification	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	not provided	CeGaT Center for Human Genetics Tuebingen Accession: SCV002062910.30 First in ClinVar: Jan 29, 2022 Last updated: Jan 11, 2026	Comment: show RET: BP4, BP7 (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes Number of individuals with the variant: 3

Benign (Feb 12, 2018) C Contributing to aggregate classification	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Multiple endocrine neoplasia	Illumina Laboratory Services, Illumina Accession: SCV001259551.1 First in ClinVar: May 31, 2020 Last updated: May 31, 2020	Comment: show This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (Feb 12, 2018) C Contributing to aggregate classification	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Pheochromocytoma	Illumina Laboratory Services, Illumina Accession: SCV001259552.1 First in ClinVar: May 31, 2020 Last updated: May 31, 2020	Comment: show This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Likely benign (Feb 12, 2018) C Contributing to aggregate classification	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Renal hypodysplasia/aplasia 1	Illumina Laboratory Services, Illumina Accession: SCV001261664.1 First in ClinVar: May 31, 2020 Last updated: May 31, 2020	Comment: show This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Likely benign (Feb 12, 2018) C Contributing to aggregate classification	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Hirschsprung disease, susceptibility to, 1	Illumina Laboratory Services, Illumina Accession: SCV001261665.1 First in ClinVar: May 31, 2020 Last updated: May 31, 2020	Comment: show This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Likely benign (Feb 05, 2016) C Contributing to aggregate classification	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Hereditary cancer-predisposing syndrome	Ambry Genetics Accession: SCV000674773.5 First in ClinVar: Jan 01, 2018 Last updated: May 01, 2024	Comment: show This alteration is classified as likely 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. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (Feb 01, 2025) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Pheochromocytoma	KCCC/NGS Laboratory, Kuwait Cancer Control Center Accession: SCV005881248.1 First in ClinVar: Mar 16, 2025 Last updated: Mar 16, 2025	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: no Observation 1 Collection method: clinical testing Allele origin: germline Affected status: no

Benign (Feb 27, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Multiple endocrine neoplasia type 2A	Myriad Genetics, Inc. Accession: SCV006096124.1 First in ClinVar: Jun 22, 2025 Last updated: Jun 22, 2025	Comment: show This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing. (less) Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown

Likely benign (Feb 16, 2025) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	not specified	Laboratory of Genetics, Children's Clinical University Hospital Latvia Accession: SCV006106158.1 First in ClinVar: Jul 05, 2025 Last updated: Jul 05, 2025	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Likely benign (Sep 29, 2022) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Multiple endocrine neoplasia, type 2	Color Diagnostics, LLC DBA Color Health Accession: SCV007439301.1 First in ClinVar: Feb 15, 2026 Last updated: Feb 15, 2026	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Platform type: NGS

Comment:

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.

Comment:

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.

Comment:

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.

Comment:

This alteration is classified as likely 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.

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs553418132 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Apr 13, 2026