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 affected with RET-related conditions. This variant is present in population databases (rs753446269, gnomAD 0.007%). This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 808 of the RET protein (p.Lys808Asn).
ClinVar Genomic variation as it relates to human health
NM_020975.6(RET):c.2424A>C (p.Lys808Asn)
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
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NM_020975.6(RET):c.2424A>C (p.Lys808Asn)
Variation ID: 1991970 Accession: VCV001991970.3
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 10q11.21 10: 43119562 (GRCh38) [ NCBI UCSC ] 10: 43615010 (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 Feb 8, 2023 May 1, 2024 Nov 19, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_020975.6:c.2424A>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_066124.1:p.Lys808Asn missense NM_000323.2:c.2424A>C NP_000314.1:p.Lys808Asn missense NM_001355216.2:c.1662A>C NP_001342145.1:p.Lys554Asn missense NM_001406743.1:c.2424A>C NP_001393672.1:p.Lys808Asn missense NM_001406744.1:c.2424A>C NP_001393673.1:p.Lys808Asn missense NM_001406759.1:c.2424A>C NP_001393688.1:p.Lys808Asn missense NM_001406760.1:c.2424A>C NP_001393689.1:p.Lys808Asn missense NM_001406761.1:c.2295A>C NP_001393690.1:p.Lys765Asn missense NM_001406762.1:c.2295A>C NP_001393691.1:p.Lys765Asn missense NM_001406763.1:c.2289A>C NP_001393692.1:p.Lys763Asn missense NM_001406764.1:c.2295A>C NP_001393693.1:p.Lys765Asn missense NM_001406765.1:c.2289A>C NP_001393694.1:p.Lys763Asn missense NM_001406766.1:c.2136A>C NP_001393695.1:p.Lys712Asn missense NM_001406767.1:c.2136A>C NP_001393696.1:p.Lys712Asn missense NM_001406768.1:c.2160A>C NP_001393697.1:p.Lys720Asn missense NM_001406769.1:c.2028A>C NP_001393698.1:p.Lys676Asn missense NM_001406770.1:c.2136A>C NP_001393699.1:p.Lys712Asn missense NM_001406771.1:c.1986A>C NP_001393700.1:p.Lys662Asn missense NM_001406772.1:c.2028A>C NP_001393701.1:p.Lys676Asn missense NM_001406773.1:c.1986A>C NP_001393702.1:p.Lys662Asn missense NM_001406774.1:c.1899A>C NP_001393703.1:p.Lys633Asn missense NM_001406775.1:c.1698A>C NP_001393704.1:p.Lys566Asn missense NM_001406776.1:c.1698A>C NP_001393705.1:p.Lys566Asn missense NM_001406777.1:c.1698A>C NP_001393706.1:p.Lys566Asn missense NM_001406778.1:c.1698A>C NP_001393707.1:p.Lys566Asn missense NM_001406779.1:c.1527A>C NP_001393708.1:p.Lys509Asn missense NM_001406780.1:c.1527A>C NP_001393709.1:p.Lys509Asn missense NM_001406781.1:c.1527A>C NP_001393710.1:p.Lys509Asn missense NM_001406782.1:c.1527A>C NP_001393711.1:p.Lys509Asn missense NM_001406783.1:c.1398A>C NP_001393712.1:p.Lys466Asn missense NM_001406784.1:c.1434A>C NP_001393713.1:p.Lys478Asn missense NM_001406785.1:c.1407A>C NP_001393714.1:p.Lys469Asn missense NM_001406786.1:c.1398A>C NP_001393715.1:p.Lys466Asn missense NM_001406787.1:c.1392A>C NP_001393716.1:p.Lys464Asn missense NM_001406788.1:c.1239A>C NP_001393717.1:p.Lys413Asn missense NM_001406789.1:c.1239A>C NP_001393718.1:p.Lys413Asn missense NM_001406790.1:c.1239A>C NP_001393719.1:p.Lys413Asn missense NM_001406791.1:c.1119A>C NP_001393720.1:p.Lys373Asn missense NM_001406792.1:c.975A>C NP_001393721.1:p.Lys325Asn missense NM_001406793.1:c.975A>C NP_001393722.1:p.Lys325Asn missense NM_001406794.1:c.975A>C NP_001393723.1:p.Lys325Asn missense NM_020629.2:c.2424A>C NP_065680.1:p.Lys808Asn missense NM_020630.7:c.2424A>C NP_065681.1:p.Lys808Asn missense NC_000010.11:g.43119562A>C NC_000010.10:g.43615010A>C NG_007489.1:g.47494A>C LRG_518:g.47494A>C LRG_518t1:c.2424A>C LRG_518p1:p.Lys808Asn LRG_518t2:c.2424A>C LRG_518p2:p.Lys808Asn - Protein change
- K464N, K662N, K676N, K765N, K808N, K325N, K413N, K466N, K469N, K566N, K554N, K633N, K373N, K478N, K509N, K712N, K720N, K763N
- Other names
- -
- Canonical SPDI
- NC_000010.11:43119561:A:C
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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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- 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 22, 2022 | RCV002814259.3 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Nov 19, 2023 | RCV004064842.1 |
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. |
|
|---|---|---|---|---|---|
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Uncertain significance
(Feb 22, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Multiple endocrine neoplasia, type 2
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV003034178.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 28, 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 affected with RET-related conditions. This variant is present in population databases (rs753446269, gnomAD 0.007%). This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 808 of the RET protein (p.Lys808Asn). (less)
|
|
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Uncertain significance
(Nov 19, 2023)
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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
|
Ambry Genetics
Accession: SCV005028267.1
First in ClinVar: May 01, 2024 Last updated: May 01, 2024 |
Comment:
The p.K808N variant (also known as c.2424A>C), located in coding exon 14 of the RET gene, results from an A to C substitution at nucleotide … (more)
The p.K808N variant (also known as c.2424A>C), located in coding exon 14 of the RET gene, results from an A to C substitution at nucleotide position 2424. The lysine at codon 808 is replaced by asparagine, an amino acid with similar properties. This amino acid position is conserved. 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)
|
Comment:
Comment:
The p.K808N variant (also known as c.2424A>C), located in coding exon 14 of the RET gene, results from an A to C substitution at nucleotide position 2424. The lysine at codon 808 is replaced by asparagine, an amino acid with similar properties. This amino acid position is conserved. 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.
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 affected with RET-related conditions. This variant is present in population databases (rs753446269, gnomAD 0.007%). This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 808 of the RET protein (p.Lys808Asn).
Comment:
The p.K808N variant (also known as c.2424A>C), located in coding exon 14 of the RET gene, results from an A to C substitution at nucleotide position 2424. The lysine at codon 808 is replaced by asparagine, an amino acid with similar properties. This amino acid position is conserved. 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.
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 this variant ...
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.