ClinVar Genomic variation as it relates to human health
NM_020975.6(RET):c.1871A>G (p.Asp624Gly)
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.
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_020975.6(RET):c.1871A>G (p.Asp624Gly)
Variation ID: 477329 Accession: VCV000477329.11
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 10q11.21 10: 43113667 (GRCh38) [ NCBI UCSC ] 10: 43609115 (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 Dec 26, 2017 May 1, 2024 Feb 20, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_020975.6:c.1871A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_066124.1:p.Asp624Gly missense NM_000323.2:c.1871A>G NP_000314.1:p.Asp624Gly missense NM_001355216.2:c.1109A>G NP_001342145.1:p.Asp370Gly missense NM_001406743.1:c.1871A>G NP_001393672.1:p.Asp624Gly missense NM_001406744.1:c.1871A>G NP_001393673.1:p.Asp624Gly missense NM_001406759.1:c.1871A>G NP_001393688.1:p.Asp624Gly missense NM_001406760.1:c.1871A>G NP_001393689.1:p.Asp624Gly missense NM_001406761.1:c.1742A>G NP_001393690.1:p.Asp581Gly missense NM_001406762.1:c.1742A>G NP_001393691.1:p.Asp581Gly missense NM_001406763.1:c.1871A>G NP_001393692.1:p.Asp624Gly missense NM_001406764.1:c.1742A>G NP_001393693.1:p.Asp581Gly missense NM_001406765.1:c.1871A>G NP_001393694.1:p.Asp624Gly missense NM_001406766.1:c.1583A>G NP_001393695.1:p.Asp528Gly missense NM_001406767.1:c.1583A>G NP_001393696.1:p.Asp528Gly missense NM_001406768.1:c.1742A>G NP_001393697.1:p.Asp581Gly missense NM_001406769.1:c.1475A>G NP_001393698.1:p.Asp492Gly missense NM_001406770.1:c.1583A>G NP_001393699.1:p.Asp528Gly missense NM_001406771.1:c.1433A>G NP_001393700.1:p.Asp478Gly missense NM_001406772.1:c.1475A>G NP_001393701.1:p.Asp492Gly missense NM_001406773.1:c.1433A>G NP_001393702.1:p.Asp478Gly missense NM_001406774.1:c.1346A>G NP_001393703.1:p.Asp449Gly missense NM_001406775.1:c.1145A>G NP_001393704.1:p.Asp382Gly missense NM_001406776.1:c.1145A>G NP_001393705.1:p.Asp382Gly missense NM_001406777.1:c.1145A>G NP_001393706.1:p.Asp382Gly missense NM_001406778.1:c.1145A>G NP_001393707.1:p.Asp382Gly missense NM_001406779.1:c.974A>G NP_001393708.1:p.Asp325Gly missense NM_001406780.1:c.974A>G NP_001393709.1:p.Asp325Gly missense NM_001406781.1:c.974A>G NP_001393710.1:p.Asp325Gly missense NM_001406782.1:c.974A>G NP_001393711.1:p.Asp325Gly missense NM_001406783.1:c.845A>G NP_001393712.1:p.Asp282Gly missense NM_001406784.1:c.881A>G NP_001393713.1:p.Asp294Gly missense NM_001406786.1:c.845A>G NP_001393715.1:p.Asp282Gly missense NM_001406787.1:c.974A>G NP_001393716.1:p.Asp325Gly missense NM_001406788.1:c.686A>G NP_001393717.1:p.Asp229Gly missense NM_001406789.1:c.686A>G NP_001393718.1:p.Asp229Gly missense NM_001406790.1:c.686A>G NP_001393719.1:p.Asp229Gly missense NM_001406792.1:c.422A>G NP_001393721.1:p.Asp141Gly missense NM_001406793.1:c.422A>G NP_001393722.1:p.Asp141Gly missense NM_001406794.1:c.422A>G NP_001393723.1:p.Asp141Gly missense NM_020629.2:c.1871A>G NP_065680.1:p.Asp624Gly missense NM_020630.7:c.1871A>G NP_065681.1:p.Asp624Gly missense NC_000010.11:g.43113667A>G NC_000010.10:g.43609115A>G NG_007489.1:g.41599A>G LRG_518:g.41599A>G LRG_518t1:c.1871A>G LRG_518p1:p.Asp624Gly LRG_518t2:c.1871A>G LRG_518p2:p.Asp624Gly - Protein change
- D624G, D370G, D229G, D325G, D382G, D492G, D528G, D141G, D449G, D282G, D294G, D478G, D581G
- Other names
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- Canonical SPDI
- NC_000010.11:43113666:A:G
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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
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The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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. |
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RET | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
3592 | 3714 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
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Jun 26, 2023 | RCV000527191.8 | |
Uncertain significance (1) |
criteria provided, single submitter
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Feb 20, 2024 | RCV001013414.4 |
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
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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
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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
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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. |
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Uncertain significance
(Feb 14, 2023)
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criteria provided, single submitter
Method: clinical testing
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Multiple endocrine neoplasia, type 2
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000658422.4
First in ClinVar: Dec 26, 2017 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: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 477329). This variant has not been reported in the literature in individuals affected with RET-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 624 of the RET protein (p.Asp624Gly). (less)
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Uncertain Significance
(Jun 26, 2023)
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criteria provided, single submitter
Method: clinical testing
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Multiple endocrine neoplasia, type 2
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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All of Us Research Program, National Institutes of Health
Accession: SCV004832645.1
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)
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Comment:
This missense variant replaces aspartic acid with glycine at codon 624 of the RET protein. Computational prediction is inconclusive regarding the impact of this variant … (more)
This missense variant replaces aspartic acid with glycine at codon 624 of the RET protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with RET-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. (less)
Number of individuals with the variant: 1
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Uncertain significance
(Feb 20, 2024)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV001173995.4
First in ClinVar: Mar 16, 2020 Last updated: May 01, 2024 |
Comment:
The p.D624G variant (also known as c.1871A>G), located in coding exon 10 of the RET gene, results from an A to G substitution at nucleotide … (more)
The p.D624G variant (also known as c.1871A>G), located in coding exon 10 of the RET gene, results from an A to G substitution at nucleotide position 1871. The aspartic acid at codon 624 is replaced by glycine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (less)
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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. |
Citations for germline classification of this variant
HelpThere 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 rs1224456563 ...
HelpRecord 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.