This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 777 of the TNK2 protein (p.Ser777Gly). This variant is present in population databases (rs139797100, gnomAD 0.2%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with TNK2-related conditions. ClinVar contains an entry for this variant (Variation ID: 259874). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.
ClinVar Genomic variation as it relates to human health
NM_001382273.1(TNK2):c.2140A>G (p.Ser714Gly)
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_001382273.1(TNK2):c.2140A>G (p.Ser714Gly)
Variation ID: 259874 Accession: VCV000259874.5
- Type and length
-
single nucleotide variant, 1 bp
- Location
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Cytogenetic: 3q29 3: 195868158 (GRCh38) [ NCBI UCSC ] 3: 195595029 (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 3, 2016 May 1, 2024 Oct 11, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001382273.1:c.2140A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001369202.1:p.Ser714Gly missense NM_001010938.1:c.2329A>G NM_001010938.2:c.2212A>G NP_001010938.2:p.Ser738Gly missense NM_001308046.2:c.2191A>G NP_001294975.1:p.Ser731Gly missense NM_001382271.1:c.2191A>G NP_001369200.1:p.Ser731Gly missense NM_001382272.1:c.2212A>G NP_001369201.1:p.Ser738Gly missense NM_001382274.1:c.2140A>G NP_001369203.1:p.Ser714Gly missense NM_001382275.1:c.2236A>G NP_001369204.1:p.Ser746Gly missense NM_001386164.1:c.2095A>G NP_001373093.1:p.Ser699Gly missense NM_001387707.1:c.2236A>G NP_001374636.1:p.Ser746Gly missense NM_001387708.1:c.2167A>G NP_001374637.1:p.Ser723Gly missense NM_001387709.1:c.2095A>G NP_001374638.1:p.Ser699Gly missense NM_001387710.1:c.2095A>G NP_001374639.1:p.Ser699Gly missense NM_001387711.1:c.2095A>G NP_001374640.1:p.Ser699Gly missense NM_001387712.1:c.2095A>G NP_001374641.1:p.Ser699Gly missense NM_001387713.1:c.2095A>G NP_001374642.1:p.Ser699Gly missense NM_001387714.1:c.2095A>G NP_001374643.1:p.Ser699Gly missense NM_001387715.1:c.2167A>G NP_001374644.1:p.Ser723Gly missense NM_001387716.1:c.2140A>G NP_001374645.1:p.Ser714Gly missense NM_001387717.1:c.2140A>G NP_001374646.1:p.Ser714Gly missense NM_001387718.1:c.2140A>G NP_001374647.1:p.Ser714Gly missense NM_001387719.1:c.2095A>G NP_001374648.1:p.Ser699Gly missense NM_001387720.1:c.2095A>G NP_001374649.1:p.Ser699Gly missense NM_001387721.1:c.2095A>G NP_001374650.1:p.Ser699Gly missense NM_005781.5:c.2095A>G NP_005772.3:p.Ser699Gly missense NR_170678.1:n.2387A>G non-coding transcript variant NR_170679.1:n.2691A>G non-coding transcript variant NR_170680.1:n.2398A>G non-coding transcript variant NR_170681.1:n.2353A>G non-coding transcript variant NR_170682.1:n.2665A>G non-coding transcript variant NR_170683.1:n.2620A>G non-coding transcript variant NR_170684.1:n.2033A>G non-coding transcript variant NR_170685.1:n.2536A>G non-coding transcript variant NR_170686.1:n.2404A>G non-coding transcript variant NR_170687.1:n.2379A>G non-coding transcript variant NR_170688.1:n.2620A>G non-coding transcript variant NR_170689.1:n.2134A>G non-coding transcript variant NR_170690.1:n.1945A>G non-coding transcript variant NR_170691.1:n.2292A>G non-coding transcript variant NR_170692.1:n.1902A>G non-coding transcript variant NC_000003.12:g.195868158T>C NC_000003.11:g.195595029T>C NG_029779.1:g.45852A>G - Protein change
- S699G, S738G, S731G, S714G, S723G, S746G
- Other names
- -
- Canonical SPDI
- NC_000003.12:195868157:T:C
-
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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0.00040 (C)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
The Genome Aggregation Database (gnomAD), exomes 0.00010
Exome Aggregation Consortium (ExAC) 0.00012
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00015
1000 Genomes Project 30x 0.00031
The Genome Aggregation Database (gnomAD) 0.00035
1000 Genomes Project 0.00040
Trans-Omics for Precision Medicine (TOPMed) 0.00046
- 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. |
|||
| TNK2 | - | - |
GRCh38 GRCh37 |
326 | 385 | |
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. |
|---|---|---|---|---|
| Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
|
Oct 12, 2021 | RCV000248150.6 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Oct 11, 2023 | RCV002518634.4 |
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
(-)
|
criteria provided, single submitter
Method: clinical testing
|
NOT SPECIFIED
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV000311268.1
First in ClinVar: Oct 03, 2016 Last updated: Oct 03, 2016 |
|
|
|
Uncertain significance
(Oct 11, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV003226771.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 20, 2024 |
Comment:
This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 777 of the TNK2 protein (p.Ser777Gly). … (more)
This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 777 of the TNK2 protein (p.Ser777Gly). This variant is present in population databases (rs139797100, gnomAD 0.2%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with TNK2-related conditions. ClinVar contains an entry for this variant (Variation ID: 259874). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. (less)
|
|
|
Uncertain significance
(Oct 12, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV004968209.1
First in ClinVar: May 01, 2024 Last updated: May 01, 2024 |
Comment:
The c.2329A>G (p.S777G) alteration is located in exon 13 (coding exon 13) of the TNK2 gene. This alteration results from a A to G substitution … (more)
The c.2329A>G (p.S777G) alteration is located in exon 13 (coding exon 13) of the TNK2 gene. This alteration results from a A to G substitution at nucleotide position 2329, causing the serine (S) at amino acid position 777 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. (less)
|
Comment:
Comment:
The c.2329A>G (p.S777G) alteration is located in exon 13 (coding exon 13) of the TNK2 gene. This alteration results from a A to G substitution at nucleotide position 2329, causing the serine (S) at amino acid position 777 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, 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:
This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 777 of the TNK2 protein (p.Ser777Gly). This variant is present in population databases (rs139797100, gnomAD 0.2%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with TNK2-related conditions. ClinVar contains an entry for this variant (Variation ID: 259874). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.
Comment:
The c.2329A>G (p.S777G) alteration is located in exon 13 (coding exon 13) of the TNK2 gene. This alteration results from a A to G substitution at nucleotide position 2329, causing the serine (S) at amino acid position 777 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, 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 rs139797100 ...
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.