The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with RET-related conditions. This variant, c.43_51del, results in the deletion of 3 amino acid(s) of the RET protein (p.Leu17_Leu19del), but otherwise preserves the integrity of the reading frame.
ClinVar Genomic variation as it relates to human health
NM_020975.6(RET):c.43_51del (p.Leu17_Leu19del)
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.
(3)
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.
Conflicting classifications of pathogenicity
Uncertain significance(2); Likely benign(1)
Uncertain significance(2); Likely benign(1)
3
criteria provided, conflicting classifications
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_020975.6(RET):c.43_51del (p.Leu17_Leu19del)
Variation ID: 580433 Accession: VCV000580433.10
- Type and length
-
Deletion, 9 bp
- Location
-
Cytogenetic: 10q11.21 10: 43077295-43077303 (GRCh38) [ NCBI UCSC ] 10: 43572743-43572751 (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 Oct 10, 2018 May 1, 2024 Nov 30, 2023 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_020975.6:c.43_51del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_066124.1:p.Leu17_Leu19del inframe deletion NM_000323.2:c.43_51delTTGCTGCTG NP_000314.1:p.Leu17_Leu19del inframe indel NM_001406743.1:c.43_51delTTGCTGCTG NP_001393672.1:p.Leu17_Leu19del inframe indel NM_001406744.1:c.43_51delTTGCTGCTG NP_001393673.1:p.Leu17_Leu19del inframe indel NM_001406759.1:c.43_51delTTGCTGCTG NP_001393688.1:p.Leu17_Leu19del inframe indel NM_001406760.1:c.43_51delTTGCTGCTG NP_001393689.1:p.Leu17_Leu19del inframe indel NM_001406761.1:c.43_51delTTGCTGCTG NP_001393690.1:p.Leu17_Leu19del inframe indel NM_001406762.1:c.43_51delTTGCTGCTG NP_001393691.1:p.Leu17_Leu19del inframe indel NM_001406763.1:c.43_51delTTGCTGCTG NP_001393692.1:p.Leu17_Leu19del inframe indel NM_001406764.1:c.43_51delTTGCTGCTG NP_001393693.1:p.Leu17_Leu19del inframe indel NM_001406765.1:c.43_51delTTGCTGCTG NP_001393694.1:p.Leu17_Leu19del inframe indel NM_001406766.1:c.43_51delTTGCTGCTG NP_001393695.1:p.Leu17_Leu19del inframe indel NM_001406767.1:c.43_51delTTGCTGCTG NP_001393696.1:p.Leu17_Leu19del inframe indel NM_001406768.1:c.43_51delTTGCTGCTG NP_001393697.1:p.Leu17_Leu19del inframe indel NM_001406769.1:c.43_51delTTGCTGCTG NP_001393698.1:p.Leu17_Leu19del inframe indel NM_001406770.1:c.43_51delTTGCTGCTG NP_001393699.1:p.Leu17_Leu19del inframe indel NM_001406771.1:c.43_51delTTGCTGCTG NP_001393700.1:p.Leu17_Leu19del inframe indel NM_001406772.1:c.43_51delTTGCTGCTG NP_001393701.1:p.Leu17_Leu19del inframe indel NM_001406773.1:c.43_51delTTGCTGCTG NP_001393702.1:p.Leu17_Leu19del inframe indel NM_001406774.1:c.43_51delTTGCTGCTG NP_001393703.1:p.Leu17_Leu19del inframe indel NM_001406775.1:c.43_51delTTGCTGCTG NP_001393704.1:p.Leu17_Leu19del inframe indel NM_001406776.1:c.43_51delTTGCTGCTG NP_001393705.1:p.Leu17_Leu19del inframe indel NM_001406777.1:c.43_51delTTGCTGCTG NP_001393706.1:p.Leu17_Leu19del inframe indel NM_001406778.1:c.43_51delTTGCTGCTG NP_001393707.1:p.Leu17_Leu19del inframe indel NM_001406779.1:c.43_51delTTGCTGCTG NP_001393708.1:p.Leu17_Leu19del inframe indel NM_001406780.1:c.43_51delTTGCTGCTG NP_001393709.1:p.Leu17_Leu19del inframe indel NM_001406781.1:c.43_51delTTGCTGCTG NP_001393710.1:p.Leu17_Leu19del inframe indel NM_001406782.1:c.43_51delTTGCTGCTG NP_001393711.1:p.Leu17_Leu19del inframe indel NM_001406783.1:c.43_51delTTGCTGCTG NP_001393712.1:p.Leu17_Leu19del inframe indel NM_001406784.1:c.43_51delTTGCTGCTG NP_001393713.1:p.Leu17_Leu19del inframe indel NM_001406785.1:c.43_51delTTGCTGCTG NP_001393714.1:p.Leu17_Leu19del inframe indel NM_001406786.1:c.43_51delTTGCTGCTG NP_001393715.1:p.Leu17_Leu19del inframe indel NM_001406787.1:c.43_51delTTGCTGCTG NP_001393716.1:p.Leu17_Leu19del inframe indel NM_001406788.1:c.43_51delTTGCTGCTG NP_001393717.1:p.Leu17_Leu19del inframe indel NM_001406789.1:c.43_51delTTGCTGCTG NP_001393718.1:p.Leu17_Leu19del inframe indel NM_001406790.1:c.43_51delTTGCTGCTG NP_001393719.1:p.Leu17_Leu19del inframe indel NM_001406791.1:c.43_51delTTGCTGCTG NP_001393720.1:p.Leu17_Leu19del inframe indel NM_001406792.1:c.43_51delTTGCTGCTG NP_001393721.1:p.Leu17_Leu19del inframe indel NM_001406793.1:c.43_51delTTGCTGCTG NP_001393722.1:p.Leu17_Leu19del inframe indel NM_001406794.1:c.43_51delTTGCTGCTG NP_001393723.1:p.Leu17_Leu19del inframe indel NM_020629.2:c.43_51delTTGCTGCTG NP_065680.1:p.Leu17_Leu19del inframe indel NM_020630.7:c.43_51delTTGCTGCTG NP_065681.1:p.Leu17_Leu19del inframe indel NC_000010.11:g.43077301_43077309del NC_000010.10:g.43572749_43572757del NG_007489.1:g.5233_5241del NG_045003.1:g.4488_4496del LRG_518:g.5233_5241del LRG_518t1:c.43_51del LRG_518p1:p.Leu17_Leu19del LRG_518t2:c.43_51del LRG_518p2:p.Leu17_Leu19del - Protein change
- -
- Other names
- -
- Canonical SPDI
- NC_000010.11:43077294:CTGCTGTTGCTGCTG:CTGCTG
-
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.
- -
- 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 |
3598 | 3720 | |
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 (2) |
criteria provided, multiple submitters, no conflicts
|
Nov 30, 2023 | RCV000703975.9 | |
| Likely benign (1) |
criteria provided, single submitter
|
Sep 15, 2020 | RCV002332497.2 |
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
(Sep 25, 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: SCV000832906.4
First in ClinVar: Oct 10, 2018 Last updated: Feb 14, 2024 |
Comment:
The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. … (more)
The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with RET-related conditions. This variant, c.43_51del, results in the deletion of 3 amino acid(s) of the RET protein (p.Leu17_Leu19del), but otherwise preserves the integrity of the reading frame. (less)
|
|
|
Uncertain Significance
(Nov 30, 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: SCV004843127.1
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: 1
Zygosity: Single Heterozygote
|
|
|
Likely benign
(Sep 15, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV002630884.2
First in ClinVar: Nov 29, 2022 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:
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.
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:
The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with RET-related conditions. This variant, c.43_51del, results in the deletion of 3 amino acid(s) of the RET protein (p.Leu17_Leu19del), but otherwise preserves the integrity of the reading frame.
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 rs1488217326 ...
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.