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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with RET-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change replaces alanine with threonine at codon 807 of the RET protein (p.Ala807Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine.
ClinVar Genomic variation as it relates to human health
NM_020975.6(RET):c.2419G>A (p.Ala807Thr)
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.
(2)
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.
Uncertain significance
2
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.2419G>A (p.Ala807Thr)
Variation ID: 1424992 Accession: VCV001424992.8
- Type and length
-
single nucleotide variant, 1 bp
- Location
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Cytogenetic: 10q11.21 10: 43119557 (GRCh38) [ NCBI UCSC ] 10: 43615005 (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 Mar 28, 2022 Jun 17, 2024 Mar 8, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_020975.6:c.2419G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_066124.1:p.Ala807Thr missense NM_000323.2:c.2419G>A NP_000314.1:p.Ala807Thr missense NM_001355216.2:c.1657G>A NP_001342145.1:p.Ala553Thr missense NM_001406743.1:c.2419G>A NP_001393672.1:p.Ala807Thr missense NM_001406744.1:c.2419G>A NP_001393673.1:p.Ala807Thr missense NM_001406759.1:c.2419G>A NP_001393688.1:p.Ala807Thr missense NM_001406760.1:c.2419G>A NP_001393689.1:p.Ala807Thr missense NM_001406761.1:c.2290G>A NP_001393690.1:p.Ala764Thr missense NM_001406762.1:c.2290G>A NP_001393691.1:p.Ala764Thr missense NM_001406763.1:c.2284G>A NP_001393692.1:p.Ala762Thr missense NM_001406764.1:c.2290G>A NP_001393693.1:p.Ala764Thr missense NM_001406765.1:c.2284G>A NP_001393694.1:p.Ala762Thr missense NM_001406766.1:c.2131G>A NP_001393695.1:p.Ala711Thr missense NM_001406767.1:c.2131G>A NP_001393696.1:p.Ala711Thr missense NM_001406768.1:c.2155G>A NP_001393697.1:p.Ala719Thr missense NM_001406769.1:c.2023G>A NP_001393698.1:p.Ala675Thr missense NM_001406770.1:c.2131G>A NP_001393699.1:p.Ala711Thr missense NM_001406771.1:c.1981G>A NP_001393700.1:p.Ala661Thr missense NM_001406772.1:c.2023G>A NP_001393701.1:p.Ala675Thr missense NM_001406773.1:c.1981G>A NP_001393702.1:p.Ala661Thr missense NM_001406774.1:c.1894G>A NP_001393703.1:p.Ala632Thr missense NM_001406775.1:c.1693G>A NP_001393704.1:p.Ala565Thr missense NM_001406776.1:c.1693G>A NP_001393705.1:p.Ala565Thr missense NM_001406777.1:c.1693G>A NP_001393706.1:p.Ala565Thr missense NM_001406778.1:c.1693G>A NP_001393707.1:p.Ala565Thr missense NM_001406779.1:c.1522G>A NP_001393708.1:p.Ala508Thr missense NM_001406780.1:c.1522G>A NP_001393709.1:p.Ala508Thr missense NM_001406781.1:c.1522G>A NP_001393710.1:p.Ala508Thr missense NM_001406782.1:c.1522G>A NP_001393711.1:p.Ala508Thr missense NM_001406783.1:c.1393G>A NP_001393712.1:p.Ala465Thr missense NM_001406784.1:c.1429G>A NP_001393713.1:p.Ala477Thr missense NM_001406785.1:c.1402G>A NP_001393714.1:p.Ala468Thr missense NM_001406786.1:c.1393G>A NP_001393715.1:p.Ala465Thr missense NM_001406787.1:c.1387G>A NP_001393716.1:p.Ala463Thr missense NM_001406788.1:c.1234G>A NP_001393717.1:p.Ala412Thr missense NM_001406789.1:c.1234G>A NP_001393718.1:p.Ala412Thr missense NM_001406790.1:c.1234G>A NP_001393719.1:p.Ala412Thr missense NM_001406791.1:c.1114G>A NP_001393720.1:p.Ala372Thr missense NM_001406792.1:c.970G>A NP_001393721.1:p.Ala324Thr missense NM_001406793.1:c.970G>A NP_001393722.1:p.Ala324Thr missense NM_001406794.1:c.970G>A NP_001393723.1:p.Ala324Thr missense NM_020629.2:c.2419G>A NP_065680.1:p.Ala807Thr missense NM_020630.7:c.2419G>A NP_065681.1:p.Ala807Thr missense NC_000010.11:g.43119557G>A NC_000010.10:g.43615005G>A NG_007489.1:g.47489G>A LRG_518:g.47489G>A LRG_518t1:c.2419G>A LRG_518p1:p.Ala807Thr LRG_518t2:c.2419G>A LRG_518p2:p.Ala807Thr - Protein change
- A807T, A553T, A412T, A468T, A711T, A719T, A324T, A508T, A675T, A762T, A764T, A372T, A565T, A632T, A463T, A465T, A477T, A661T
- Other names
- -
- Canonical SPDI
- NC_000010.11:43119556:G:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
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.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
Exome Aggregation Consortium (ExAC) 0.00001
- 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. |
|---|---|---|---|---|
| Uncertain significance (1) |
criteria provided, single submitter
|
Feb 14, 2021 | RCV001924192.7 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Mar 8, 2024 | RCV004571627.1 |
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. |
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. |
|
|---|---|---|---|---|---|
|
Uncertain significance
(Feb 14, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Multiple endocrine neoplasia, type 2
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV002200379.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 20, 2024 |
Comment:
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 … (more)
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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with RET-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change replaces alanine with threonine at codon 807 of the RET protein (p.Ala807Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. (less)
|
|
|
Uncertain significance
(Mar 08, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Hirschsprung disease, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV005054179.1
First in ClinVar: Jun 17, 2024 Last updated: Jun 17, 2024 |
|
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:
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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with RET-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change replaces alanine with threonine at codon 807 of the RET protein (p.Ala807Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine.
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 rs760012685 ...
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.