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.
ClinVar Genomic variation as it relates to human health
NM_020975.6(RET):c.2226G>A (p.Thr742=)
Germline
Classification
Help
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.
(8)
Help
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Benign/Likely benign
8
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_020975.6(RET):c.2226G>A (p.Thr742=)
Variation ID: 220507 Accession: VCV000220507.19
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 10q11.21 10: 43116673 (GRCh38) [ NCBI UCSC ] 10: 43612121 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 6, 2017 May 1, 2024 Jan 9, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_020975.6:c.2226G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_066124.1:p.Thr742= synonymous NM_000323.2:c.2226G>A NP_000314.1:p.Thr742= synonymous NM_001355216.2:c.1464G>A NP_001342145.1:p.Thr488= synonymous NM_001406743.1:c.2226G>A NP_001393672.1:p.Thr742= synonymous NM_001406744.1:c.2226G>A NP_001393673.1:p.Thr742= synonymous NM_001406759.1:c.2226G>A NP_001393688.1:p.Thr742= synonymous NM_001406760.1:c.2226G>A NP_001393689.1:p.Thr742= synonymous NM_001406761.1:c.2097G>A NP_001393690.1:p.Thr699= synonymous NM_001406762.1:c.2097G>A NP_001393691.1:p.Thr699= synonymous NM_001406763.1:c.2091G>A NP_001393692.1:p.Thr697= synonymous NM_001406764.1:c.2097G>A NP_001393693.1:p.Thr699= synonymous NM_001406765.1:c.2091G>A NP_001393694.1:p.Thr697= synonymous NM_001406766.1:c.1938G>A NP_001393695.1:p.Thr646= synonymous NM_001406767.1:c.1938G>A NP_001393696.1:p.Thr646= synonymous NM_001406768.1:c.1962G>A NP_001393697.1:p.Thr654= synonymous NM_001406769.1:c.1830G>A NP_001393698.1:p.Thr610= synonymous NM_001406770.1:c.1938G>A NP_001393699.1:p.Thr646= synonymous NM_001406771.1:c.1788G>A NP_001393700.1:p.Thr596= synonymous NM_001406772.1:c.1830G>A NP_001393701.1:p.Thr610= synonymous NM_001406773.1:c.1788G>A NP_001393702.1:p.Thr596= synonymous NM_001406774.1:c.1701G>A NP_001393703.1:p.Thr567= synonymous NM_001406775.1:c.1500G>A NP_001393704.1:p.Thr500= synonymous NM_001406776.1:c.1500G>A NP_001393705.1:p.Thr500= synonymous NM_001406777.1:c.1500G>A NP_001393706.1:p.Thr500= synonymous NM_001406778.1:c.1500G>A NP_001393707.1:p.Thr500= synonymous NM_001406779.1:c.1329G>A NP_001393708.1:p.Thr443= synonymous NM_001406780.1:c.1329G>A NP_001393709.1:p.Thr443= synonymous NM_001406781.1:c.1329G>A NP_001393710.1:p.Thr443= synonymous NM_001406782.1:c.1329G>A NP_001393711.1:p.Thr443= synonymous NM_001406783.1:c.1200G>A NP_001393712.1:p.Thr400= synonymous NM_001406784.1:c.1236G>A NP_001393713.1:p.Thr412= synonymous NM_001406785.1:c.1209G>A NP_001393714.1:p.Thr403= synonymous NM_001406786.1:c.1200G>A NP_001393715.1:p.Thr400= synonymous NM_001406787.1:c.1194G>A NP_001393716.1:p.Thr398= synonymous NM_001406788.1:c.1041G>A NP_001393717.1:p.Thr347= synonymous NM_001406789.1:c.1041G>A NP_001393718.1:p.Thr347= synonymous NM_001406790.1:c.1041G>A NP_001393719.1:p.Thr347= synonymous NM_001406791.1:c.921G>A NP_001393720.1:p.Thr307= synonymous NM_001406792.1:c.777G>A NP_001393721.1:p.Thr259= synonymous NM_001406793.1:c.777G>A NP_001393722.1:p.Thr259= synonymous NM_001406794.1:c.777G>A NP_001393723.1:p.Thr259= synonymous NM_020629.2:c.2226G>A NP_065680.1:p.Thr742= synonymous NM_020630.7:c.2226G>A NP_065681.1:p.Thr742= synonymous NC_000010.11:g.43116673G>A NC_000010.10:g.43612121G>A NG_007489.1:g.44605G>A LRG_518:g.44605G>A LRG_518t1:c.2226G>A LRG_518p1:p.Thr742= LRG_518t2:c.2226G>A LRG_518p2:p.Thr742= - Protein change
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- Other names
- -
- Canonical SPDI
- NC_000010.11:43116672:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
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Global minor allele
frequency (GMAF) HelpThe 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.
- -
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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The Genome Aggregation Database (gnomAD) 0.00002
Trans-Omics for Precision Medicine (TOPMed) 0.00002
The Genome Aggregation Database (gnomAD), exomes 0.00018
Exome Aggregation Consortium (ExAC) 0.00023
- Links
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 | ||
|---|---|---|---|---|---|---|
| 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 |
3595 | 3717 | |
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. |
|---|---|---|---|---|
| Benign (2) |
criteria provided, multiple submitters, no conflicts
|
Sep 27, 2018 | RCV000205202.9 | |
| Likely benign (1) |
criteria provided, single submitter
|
Mar 2, 2016 | RCV000409060.3 | |
| Likely benign (1) |
criteria provided, single submitter
|
Mar 2, 2016 | RCV000411512.3 | |
| Benign/Likely benign (2) |
criteria provided, multiple submitters, no conflicts
|
Jan 9, 2024 | RCV001083002.11 | |
| Likely benign (2) |
criteria provided, multiple submitters, no conflicts
|
May 10, 2021 | RCV000575112.4 |
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. |
More information
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
(Mar 02, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Multiple endocrine neoplasia type 2B
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000489791.2
First in ClinVar: Jan 06, 2017 Last updated: Dec 24, 2022 |
|
|
|
Likely benign
(Mar 02, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Multiple endocrine neoplasia type 2A
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000489792.2
First in ClinVar: Jan 06, 2017 Last updated: Dec 24, 2022 |
|
|
|
Benign
(Jan 09, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Multiple endocrine neoplasia, type 2
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000261107.9
First in ClinVar: Feb 02, 2016 Last updated: Feb 28, 2024 |
|
|
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Benign
(Sep 27, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Athena Diagnostics
Accession: SCV001144499.1
First in ClinVar: Jan 18, 2020 Last updated: Jan 18, 2020 |
|
|
|
Likely benign
(May 10, 2021)
|
criteria provided, single submitter
Method: curation
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Sema4, Sema4
Accession: SCV002529966.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022 |
|
|
|
Benign
(Sep 27, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
unknown
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV004220041.1
First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 |
|
|
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Likely Benign
(Dec 18, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Multiple endocrine neoplasia, type 2
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
All of Us Research Program, National Institutes of Health
Accession: SCV004815192.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
|
Number of individuals with the variant: 8
|
|
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Likely benign
(Aug 04, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000674774.5
First in ClinVar: Jan 01, 2018 Last updated: May 01, 2024 |
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 … (more)
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)
|
Comment:
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
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
Help| 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 rs762876946 ...
HelpThese 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 Sep 29, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.