The p.Gly262fs variant in TP53 has not been previously reported in individuals with Li-Fraumeni syndrome or in large population studies. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 262 and leads to a premature termination codon 85 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. In summary, although additional studies are required to fully establish its clinical significance, the p.Gly262fs variant is likely pathogenic. ACMG/AMP Criteria applied: PVS1, PM2.
ClinVar Genomic variation as it relates to human health
NM_000546.6(TP53):c.784_785insAAGCC (p.Gly262fs)
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)
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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.
Likely 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.784_785insAAGCC (p.Gly262fs)
Variation ID: 3076058 Accession: VCV003076058.1
- Type and length
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Insertion, 5 bp
- Location
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Cytogenetic: 17p13.1 17: 7673835-7673836 (GRCh38) [ NCBI UCSC ] 17: 7577153-7577154 (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 Apr 20, 2024 Apr 20, 2024 Jun 25, 2018 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000546.6:c.784_785insAAGCC MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000537.3:p.Gly262fs frameshift NM_001126112.3:c.784_785insAAGCC NP_001119584.1:p.Gly262fs frameshift NM_001126113.3:c.784_785insAAGCC NP_001119585.1:p.Gly262fs frameshift NM_001126114.3:c.784_785insAAGCC NP_001119586.1:p.Gly262fs frameshift NM_001126115.2:c.388_389insAAGCC NP_001119587.1:p.Gly130fs frameshift NM_001126116.2:c.388_389insAAGCC NP_001119588.1:p.Gly130fs frameshift NM_001126117.2:c.388_389insAAGCC NP_001119589.1:p.Gly130fs frameshift NM_001126118.2:c.667_668insAAGCC NP_001119590.1:p.Gly223fs frameshift NM_001276695.3:c.667_668insAAGCC NP_001263624.1:p.Gly223fs frameshift NM_001276696.3:c.667_668insAAGCC NP_001263625.1:p.Gly223fs frameshift NM_001276697.3:c.307_308insAAGCC NP_001263626.1:p.Gly103fs frameshift NM_001276698.3:c.307_308insAAGCC NP_001263627.1:p.Gly103fs frameshift NM_001276699.3:c.307_308insAAGCC NP_001263628.1:p.Gly103fs frameshift NM_001276760.3:c.667_668insAAGCC NP_001263689.1:p.Gly223fs frameshift NM_001276761.3:c.667_668insAAGCC NP_001263690.1:p.Gly223fs frameshift NM_001407262.1:c.784_785insAAGCC NP_001394191.1:p.Gly262fs frameshift NM_001407263.1:c.667_668insAAGCC NP_001394192.1:p.Gly223fs frameshift NM_001407264.1:c.784_785insAAGCC NP_001394193.1:p.Gly262fs frameshift NM_001407265.1:c.667_668insAAGCC NP_001394194.1:p.Gly223fs frameshift NM_001407266.1:c.784_785insAAGCC NP_001394195.1:p.Gly262fs frameshift NM_001407267.1:c.667_668insAAGCC NP_001394196.1:p.Gly223fs frameshift NM_001407268.1:c.784_785insAAGCC NP_001394197.1:p.Gly262fs frameshift NM_001407269.1:c.667_668insAAGCC NP_001394198.1:p.Gly223fs frameshift NM_001407270.1:c.784_785insAAGCC NP_001394199.1:p.Gly262fs frameshift NM_001407271.1:c.667_668insAAGCC NP_001394200.1:p.Gly223fs frameshift NR_176326.1:n.813_814insAAGCC non-coding transcript variant NC_000017.11:g.7673835_7673836insGGCTT NC_000017.10:g.7577153_7577154insGGCTT NG_017013.2:g.18715_18716insAAGCC LRG_321:g.18715_18716insAAGCC LRG_321t1:c.784_785insAAGCC LRG_321p1:p.Gly262Glufs LRG_321t2:c.784_785insAAGCC LRG_321:p.Gly262Glufs LRG_321t3:c.784_785insAAGCC LRG_321p3:p.Gly262Glufs LRG_321t4:c.784_785insAAGCC LRG_321p4:p.Gly262Glufs LRG_321t5:c.388_389insAAGCC LRG_321p5:p.Gly130Glufs LRG_321t6:c.388_389insAAGCC LRG_321p6:p.Gly130Glufs LRG_321t7:c.388_389insAAGCC LRG_321p7:p.Gly130Glufs LRG_321t8:c.667_668insAAGCC LRG_321p8:p.Gly223Glufs - Protein change
- G103fs, G130fs, G223fs, G262fs
- Other names
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- Canonical SPDI
- NC_000017.11:7673835::GGCTT
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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. |
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| 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. |
|---|---|---|---|---|
| Likely pathogenic (1) |
criteria provided, single submitter
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Jun 25, 2018 | RCV004018376.2 |
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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Likely Pathogenic
(Jun 25, 2018)
|
criteria provided, single submitter
Method: clinical testing
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Li-Fraumeni syndrome
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV004848172.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024 |
Comment:
The p.Gly262fs variant in TP53 has not been previously reported in individuals with Li-Fraumeni syndrome or in large population studies. This variant is predicted to … (more)
The p.Gly262fs variant in TP53 has not been previously reported in individuals with Li-Fraumeni syndrome or in large population studies. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 262 and leads to a premature termination codon 85 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. In summary, although additional studies are required to fully establish its clinical significance, the p.Gly262fs variant is likely pathogenic. ACMG/AMP Criteria applied: PVS1, PM2. (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:
The p.Gly262fs variant in TP53 has not been previously reported in individuals with Li-Fraumeni syndrome or in large population studies. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 262 and leads to a premature termination codon 85 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. In summary, although additional studies are required to fully establish its clinical significance, the p.Gly262fs variant is likely pathogenic. ACMG/AMP Criteria applied: PVS1, PM2.
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 Jun 23, 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.