For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with TP53-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Asn263Thrfs*5) in the TP53 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TP53 are known to be pathogenic (PMID: 20522432).
ClinVar Genomic variation as it relates to human health
NM_000546.6(TP53):c.786_796del (p.Asn263fs)
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.
(1)
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.
Pathogenic
1
criteria provided, single submitter
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000546.6(TP53):c.786_796del (p.Asn263fs)
Variation ID: 2809259 Accession: VCV002809259.1
- Type and length
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Deletion, 11 bp
- Location
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Cytogenetic: 17p13.1 17: 7673824-7673834 (GRCh38) [ NCBI UCSC ] 17: 7577142-7577152 (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 20, 2024 Feb 20, 2024 Oct 21, 2022 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000546.6:c.786_796del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000537.3:p.Asn263fs frameshift NM_001126112.3:c.786_796del NP_001119584.1:p.Asn263fs frameshift NM_001126113.3:c.786_796del NP_001119585.1:p.Asn263fs frameshift NM_001126114.3:c.786_796del NP_001119586.1:p.Asn263fs frameshift NM_001126115.2:c.390_400del NP_001119587.1:p.Asn131fs frameshift NM_001126116.2:c.390_400del NP_001119588.1:p.Asn131fs frameshift NM_001126117.2:c.390_400del NP_001119589.1:p.Asn131fs frameshift NM_001126118.2:c.669_679del NP_001119590.1:p.Asn224fs frameshift NM_001276695.3:c.669_679del NP_001263624.1:p.Asn224fs frameshift NM_001276696.3:c.669_679del NP_001263625.1:p.Asn224fs frameshift NM_001276697.3:c.309_319del NP_001263626.1:p.Asn104fs frameshift NM_001276698.3:c.309_319del NP_001263627.1:p.Asn104fs frameshift NM_001276699.3:c.309_319del NP_001263628.1:p.Asn104fs frameshift NM_001276760.3:c.669_679del NP_001263689.1:p.Asn224fs frameshift NM_001276761.3:c.669_679del NP_001263690.1:p.Asn224fs frameshift NM_001407262.1:c.786_796del NP_001394191.1:p.Asn263fs frameshift NM_001407263.1:c.669_679del NP_001394192.1:p.Asn224fs frameshift NM_001407264.1:c.786_796del NP_001394193.1:p.Asn263fs frameshift NM_001407265.1:c.669_679del NP_001394194.1:p.Asn224fs frameshift NM_001407266.1:c.786_796del NP_001394195.1:p.Asn263fs frameshift NM_001407267.1:c.669_679del NP_001394196.1:p.Asn224fs frameshift NM_001407268.1:c.786_796del NP_001394197.1:p.Asn263fs frameshift NM_001407269.1:c.669_679del NP_001394198.1:p.Asn224fs frameshift NM_001407270.1:c.786_796del NP_001394199.1:p.Asn263fs frameshift NM_001407271.1:c.669_679del NP_001394200.1:p.Asn224fs frameshift NR_176326.1:n.815_825del non-coding transcript variant NC_000017.11:g.7673827_7673837del NC_000017.10:g.7577145_7577155del NG_017013.2:g.18717_18727del LRG_321:g.18717_18727del LRG_321t1:c.783_793del LRG_321p1:p.Asn263Thrfs LRG_321t2:c.783_793del LRG_321:p.Asn263Thrfs LRG_321t3:c.783_793del LRG_321p3:p.Asn263Thrfs LRG_321t4:c.783_793del LRG_321p4:p.Asn263Thrfs LRG_321t5:c.387_397del LRG_321p5:p.Asn131Thrfs LRG_321t6:c.387_397del LRG_321p6:p.Asn131Thrfs LRG_321t7:c.387_397del LRG_321p7:p.Asn131Thrfs LRG_321t8:c.666_676del LRG_321p8:p.Asn224Thrfs - Protein change
- N104fs, N131fs, N224fs, N263fs
- Other names
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- Canonical SPDI
- NC_000017.11:7673823:CCAGTAGATTACCA:CCA
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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. |
|||
| TP53 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
3367 | 3466 | |
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. |
|---|---|---|---|---|
| Pathogenic (1) |
criteria provided, single submitter
|
Oct 21, 2022 | RCV003622561.2 |
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. |
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Pathogenic
(Oct 21, 2022)
|
criteria provided, single submitter
Method: clinical testing
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Li-Fraumeni syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV004404801.1
First in ClinVar: Feb 20, 2024 Last updated: Feb 20, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with TP53-related conditions. … (more)
For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with TP53-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Asn263Thrfs*5) in the TP53 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TP53 are known to be pathogenic (PMID: 20522432). (less)
|
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:
For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with TP53-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Asn263Thrfs*5) in the TP53 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TP53 are known to be pathogenic (PMID: 20522432).
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| TP53 germline mutation testing in 180 families suspected of Li-Fraumeni syndrome: mutation detection rate and relative frequency of cancers in different familial phenotypes. | Ruijs MW | Journal of medical genetics | 2010 | PMID: 20522432 |
Text-mined citations for this variant ...
HelpRecord last updated Sep 30, 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.