ClinVar Genomic variation as it relates to human health
NM_000546.6(TP53):c.215C>G (p.Pro72Arg)
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.
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.
No data submitted for somatic clinical impact
The aggregate oncogenicity classification for this variant for one or more tumor types, using the ClinGen/CGC/VICC terminology. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate oncogenicity 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.
Variant Details
- Identifiers
-
NM_000546.6(TP53):c.215C>G (p.Pro72Arg)
Variation ID: 12351 Accession: VCV000012351.73
- Type and length
-
single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17p13.1 17: 7676154 (GRCh38) [ NCBI UCSC ] 17: 7579472 (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 Apr 12, 2013 Dec 14, 2024 Oct 3, 2024 Somatic - Oncogenicity Aug 11, 2024 Aug 11, 2024 Jul 31, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_000546.6:c.215C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000537.3:p.Pro72Arg missense NM_001126112.3:c.215C>G NP_001119584.1:p.Pro72Arg missense NM_001126113.3:c.215C>G NP_001119585.1:p.Pro72Arg missense NM_001126114.3:c.215C>G NP_001119586.1:p.Pro72Arg missense NM_001126118.2:c.98C>G NP_001119590.1:p.Pro33Arg missense NM_001276695.3:c.98C>G NP_001263624.1:p.Pro33Arg missense NM_001276696.3:c.98C>G NP_001263625.1:p.Pro33Arg missense NM_001276760.3:c.98C>G NP_001263689.1:p.Pro33Arg missense NM_001276761.3:c.98C>G NP_001263690.1:p.Pro33Arg missense NC_000017.11:g.7676154G>C NC_000017.10:g.7579472G>C NG_017013.2:g.16397C>G LRG_321:g.16397C>G LRG_321t1:c.215C>G LRG_321p1:p.Pro72Arg LRG_321t3:c.215C>G LRG_321p3:p.Pro72Arg P04637:p.Pro72Arg - Protein change
- P72R, P33R
- Other names
- -
- Canonical SPDI
- NC_000017.11:7676153:G:C
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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.
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0.45707 (G)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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1000 Genomes Project 0.54293
1000 Genomes Project 30x 0.54388
Trans-Omics for Precision Medicine (TOPMed) 0.61738
The Genome Aggregation Database (gnomAD) 0.62654
Exome Aggregation Consortium (ExAC) 0.65996
The Genome Aggregation Database (gnomAD), exomes 0.66816
- 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 | ||
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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 |
3373 | 3472 |
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. |
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Benign (8) |
criteria provided, multiple submitters, no conflicts
|
Apr 5, 2016 | RCV000079202.33 | |
Pathogenic (1) |
no assertion criteria provided
|
Apr 30, 2019 | RCV001255631.9 | |
Benign (1) |
no assertion criteria provided
|
- | RCV002510562.9 | |
Benign (2) |
criteria provided, multiple submitters, no conflicts
|
Oct 3, 2024 | RCV000300782.23 | |
Benign (1) |
criteria provided, single submitter
|
Dec 20, 2021 | RCV002496335.8 | |
Benign (4) |
criteria provided, multiple submitters, no conflicts
|
Nov 30, 2023 | RCV000034639.25 | |
Benign (3) |
criteria provided, multiple submitters, no conflicts
|
Jun 18, 2022 | RCV000132165.16 | |
CODON 72 POLYMORPHISM
|
Benign (1) |
no assertion criteria provided
|
Oct 1, 2009 | RCV000013144.14 |
Benign (6) |
criteria provided, multiple submitters, no conflicts
|
Jun 18, 2022 | RCV000144668.18 | |
Benign (2) |
criteria provided, multiple submitters, no conflicts
|
Apr 19, 2022 | RCV002225263.11 |
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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Benign
(-)
|
criteria provided, single submitter
Method: clinical testing
|
NOT SPECIFIED
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV000305114.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
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Benign
(Apr 05, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000111071.8
First in ClinVar: Jan 22, 2014 Last updated: Feb 19, 2018 |
Number of individuals with the variant: 103
Zygosity: Homozygote, Single Heterozygote
Sex: mixed
|
|
Benign
(Dec 20, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Familial cancer of breast
Colorectal cancer Hepatocellular carcinoma Glioma susceptibility 1 Li-Fraumeni syndrome 1 Adrenocortical carcinoma, hereditary Bone osteosarcoma Familial pancreatic carcinoma Choroid plexus papilloma Nasopharyngeal carcinoma Basal cell carcinoma, susceptibility to, 7 Bone marrow failure syndrome 5
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV002804833.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
|
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Benign
(Feb 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Li-Fraumeni syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000629789.7
First in ClinVar: Dec 26, 2017 Last updated: Feb 14, 2024 |
|
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Benign
(Nov 18, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000187242.9
First in ClinVar: Aug 06, 2014 Last updated: May 01, 2024 |
Comment:
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation … (more)
This alteration is classified as 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)
|
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Benign
(-)
|
criteria provided, single submitter
Method: not provided
|
not provided
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Breakthrough Genomics, Breakthrough Genomics
Accession: SCV005251488.1
First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024 |
|
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Benign
(Nov 05, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000292072.1
First in ClinVar: Jul 08, 2016 Last updated: Jul 08, 2016 |
|
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Benign
(Aug 18, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Li-Fraumeni syndrome 1
Affected status: no
Allele origin:
germline
|
IntelligeneCG
Accession: SCV000611723.1
First in ClinVar: Oct 19, 2014 Last updated: Oct 19, 2014 |
|
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Benign
(Mar 06, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Li-Fraumeni syndrome 1
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000407071.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
|
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Benign
(Jan 01, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Li-Fraumeni syndrome 1
Affected status: yes
Allele origin:
unknown
|
Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV001440886.1
First in ClinVar: Oct 31, 2020 Last updated: Oct 31, 2020 |
|
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Benign
(Apr 19, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: yes
Allele origin:
germline
|
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State
Accession: SCV002505076.1
First in ClinVar: Apr 30, 2022 Last updated: Apr 30, 2022 |
Number of individuals with the variant: 179
Geographic origin: South Africa
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Benign
(Nov 01, 2021)
|
criteria provided, single submitter
Method: research
|
Hereditary breast ovarian cancer syndrome
Affected status: yes
Allele origin:
germline
|
Genetics Program, Instituto Nacional de Cancer
Accession: SCV002515178.1
First in ClinVar: Nov 19, 2022 Last updated: Nov 19, 2022 |
Geographic origin: Brazil
|
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Benign
(Jun 18, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: no
Allele origin:
germline
|
Genome-Nilou Lab
Accession: SCV002582428.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022 |
|
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Benign
(Jun 18, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Li-Fraumeni syndrome 1
Affected status: no
Allele origin:
germline
|
Genome-Nilou Lab
Accession: SCV002583090.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022 |
|
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Benign
(Mar 03, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV001940208.2
First in ClinVar: Sep 29, 2021 Last updated: Mar 04, 2023 |
Comment:
This variant is associated with the following publications: (PMID: 17719241, 22289634, 23729685, 22703879, 18990008, 22524816, 20128691, 12459171, 19657731, 15138483, 21323870, 18426989, 15183530, 20587514, 18256523, 19789321, … (more)
This variant is associated with the following publications: (PMID: 17719241, 22289634, 23729685, 22703879, 18990008, 22524816, 20128691, 12459171, 19657731, 15138483, 21323870, 18426989, 15183530, 20587514, 18256523, 19789321, 15131588, 19837266, 18567547, 23210739, 22189267, 21038427, 20019240, 23073555, 20939739, 19357867, 19521721, 20886596, 21931130, 21454683, 21814224, 22336889, 19542078, 16258005, 11983757, 19657586, 11844595, 22367371, 21245379, 9891044, 17403527, 18583979, 12567188, 19171829, 19165225, 19639206, 21124037, 23207172, 21778786, 24728327, 21283750, 22545084, 24747975, 12826609, 19470478, 8625447, 23793604, 27153395, 25896519, 15609317, 23683469, 9607760) (less)
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Benign
(Nov 30, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000605416.10
First in ClinVar: Dec 06, 2016 Last updated: Feb 20, 2024 |
|
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Benign
(Oct 03, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Li-Fraumeni syndrome
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
All of Us Research Program, National Institutes of Health
Accession: SCV004823832.2
First in ClinVar: Apr 20, 2024 Last updated: Dec 14, 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: 129232
Zygosity: Homozygote, Hemizygote, Single Heterozygote
|
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no known pathogenicity
(Jul 13, 2012)
|
no assertion criteria provided
Method: research
|
not provided
Affected status: no
Allele origin:
germline
|
Biesecker Lab/Clinical Genomics Section, National Institutes of Health
Study: ClinSeq
Accession: SCV000043503.1 First in ClinVar: Apr 12, 2013 Last updated: Apr 12, 2013 |
Comment:
Converted during submission to Benign.
Number of individuals with the variant: 369
Comment on evidence:
The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:22703879 for … (more)
The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:22703879 for details. (less)
|
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Uncertain significance
(Jul 24, 2014)
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no assertion criteria provided
Method: clinical testing
|
Li-Fraumeni syndrome 1
Affected status: unknown
Allele origin:
germline
|
Pathway Genomics
Accession: SCV000189999.1
First in ClinVar: Oct 19, 2014 Last updated: Oct 19, 2014 |
|
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Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
Li-Fraumeni syndrome 1
Affected status: yes
Allele origin:
germline
|
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV000733710.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
|
|
Benign
(Oct 01, 2009)
|
no assertion criteria provided
Method: literature only
|
CODON 72 POLYMORPHISM
Affected status: not provided
Allele origin:
unknown
|
OMIM
Accession: SCV000033391.5
First in ClinVar: Apr 04, 2013 Last updated: Nov 29, 2019 |
Comment on evidence:
Ara et al. (1990) reported that the pro72-to-arg (P72R) change in p53 is caused by polymorphism rather than mutation. Olschwang et al. (1991) assessed the … (more)
Ara et al. (1990) reported that the pro72-to-arg (P72R) change in p53 is caused by polymorphism rather than mutation. Olschwang et al. (1991) assessed the frequency of the pro72-to-arg (P72R) polymorphism and, from its frequency in colon cancer patients and control subjects, concluded that there was no strong association with colon cancer. In both the cancer group and the control group, the frequencies of the pro72 and arg72 alleles were about 31 and 69%, respectively. The E6 oncoprotein derived from tumor-associated human papillomaviruses (HPVs) binds to and induces degradation of p53. Storey et al. (1998) investigated the effect of the P72R polymorphism on susceptibility of p53 to E6-mediated degradation and found that the arg72 form of p53 was significantly more susceptible than the pro72 form. Moreover, allelic analysis of patients with HPV-associated tumors revealed a striking overrepresentation of homozygous arg72 p53 compared with the normal population, indicating that individuals homozygous for arg72 are about 7 times more susceptible to HPV-associated tumorigenesis than heterozygotes. Using immunoprecipitation followed by SDS-PAGE, Thomas et al. (1999) found that the arg72 and pro72 p53 variants did not differ in their ability to bind DNA in a sequence-specific manner. They concluded that arg72 and pro72 are conformationally indistinguishable and that both can be considered wildtype. However, Thomas et al. (1999) noted that p53(pro) was a stronger inducer of transcription than p53(arg), whereas p53(arg) induced apoptosis faster and was a more potent suppressor of transformation than p53(pro). Marin et al. (2000) found that some tumor-derived p53 mutants bound and inactivated p73 (601990). The binding of such mutants was influenced by whether TP53 codon 72 encoded arginine or proline. The ability of p53 to bind p73, neutralize p73-induced apoptosis, and transform cells in cooperation with EJ-Ras (see 190020) was enhanced when codon 72 encoded arg. Marin et al. (2000) found that the arg-containing allele was preferentially mutated and retained in squamous cell tumors arising in arg/pro germline heterozygotes. They concluded that inactivation of p53 family members may contribute to the biologic properties of a subset of p53 mutants, and that a polymorphic residue within p53 affects mutant behavior. Laryngeal papillomatosis is caused by human papillomavirus and is associated with malignant transformation in 3 to 7% of cases. Aaltonen et al. (2001) found no difference in the prevalence of the P72R polymorphism between a group of patients with laryngeal papillomas and a control group. The pro72-to-arg polymorphism occurs in the proline-rich domain of p53, which is necessary for the protein to fully induce apoptosis. Dumont et al. (2003) found that in cell lines containing inducible versions of alleles encoding the pro72 and arg72 variants, and in cells with endogenous p53, the arg72 variant induced apoptosis markedly better than the pro72 variant. They suggested that at least 1 source of this enhanced apoptotic potential is the greater ability of the arg72 variant to localize to mitochondria; this localization was accompanied by release of cytochrome c into the cytosol. In 92 Caucasian MLH1 (120436) or MSH2 (609309) mutation carriers, including 47 with colorectal cancer, Jones et al. (2004) analyzed the p53 codon 72 genotype and found that arg/pro heterozygotes were 1.94 times more likely to get colorectal cancer during any age interval and developed it 13 years earlier than arg/arg homozygotes. The number of pro/pro homozygotes was too small to provide meaningful results. Kruger et al. (2005) studied the p53 genotype of 167 unrelated patients with hereditary nonpolyposis colon cancer (HNPCC; see 120435) with germline mutations in either MSH2 or MLH1 and found that the median age of onset was 41 years for arg/arg, 36 years for arg/pro, and 32 years for pro/pro individuals (p less than 0.0001). There was no difference in age of onset in 126 patients with microsatellite stable colorectal cancers. Kruger et al. (2005) concluded that in a mismatch repair-deficient background, p53 codon 72 genotypes are associated with the age of onset of colorectal carcinoma in a dose-dependent manner. Bougeard et al. (2006) studied the effect of the MDM2 SNP309 polymorphism (164785.0001) and the arg72-to-pro polymorphism of the p53 gene on cancer risk in 61 French carriers of the p53 germline mutation. The mean age of tumor onset in p53 codon 72 polymorphism arg allele carriers (21.8 years) was different from that of pro/pro patients (34.4 years, p less than 0.05). Bougeard et al. (2006) also observed a cumulative effect of both polymorphisms because the mean ages of tumor onset in carriers of MDM2 G and p53 arg alleles (16.9 years) and those with the MDM2 T/T and p53 pro/pro genotypes (43 years) were clearly different (p less than 0.02). The results confirmed the impact of the MDM2 SNP309 G allele on the age of tumor onset in germline p53 mutation carriers, and suggested that this effect may be amplified by the p53 arg72 allele. IASPP (607463) is among the most evolutionarily conserved inhibitors of p53, whereas ASPP1 (606455) and ASPP2 (602143) are activators of p53. Bergamaschi et al. (2006) showed that, in addition to the DNA-binding domain, the ASPP family members also bound to the proline-rich region of p53 containing the codon 72 polymorphism. Furthermore, the ASPP family members, particularly IASPP, bound to and regulated the activity of p53 pro72 more efficiently than that of p53 arg72. Orsted et al. (2007) stated that arg72 increases the ability of p53 to locate to mitochondria and induce cell death, whereas pro72 exhibits lower apoptotic potential but increases cellular arrest in G1 of the cell cycle. In a study of 9,219 Danish individuals, they found that overall 12-year survival was increased in p53 arg/pro heterozygotes by 3% (P of 0.003) and in pro/pro homozygotes by 6% (P of 0.002) compared with arg/arg homozygotes, corresponding to an increase in median survival of 3 years for pro/pro versus arg/arg homozygotes. Pro/pro homozygotes also showed increased survival after development of cancer, or even after development of other life-threatening diseases, compared with arg/arg homozygotes. The arg72-to-pro change was not associated with decreased risk of cancer. Among 254 patients with glioblastoma multiforme (see 137800), El Hallani et al. (2009) found an association between the pro72 allele and earlier age at onset. The pro/pro genotype was present in 20.6% of patients with onset before age 45 years, compared to in 6.5% of those with onset after age 45 years (p = 0.002) and 5.9% among 238 controls (p = 0.001). The findings were confirmed in an additional cohort of 29 patients. The variant did not have any impact on overall patient survival. Analysis of tumor DNA from 73 cases showed an association between the pro allele and a higher rate of somatic TP53 mutations. In a study of 863 individuals with European grandparents from an unselected New Zealand birth cohort, Hancox et al. (2009) analyzed lung function (FEV1 and FEV1/FVC) between ages 18 and 32 in relation to cumulative history of cigarette smoking and the rs1042522 SNP, and found that the G allele was associated with smoking-related accelerated rate of decline in lung function (see 608852) (FEV1, p = 0.020; FEV1/FVC, p = 0.037). (less)
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Pathogenic
(Apr 30, 2019)
|
no assertion criteria provided
Method: research
|
Lip and oral cavity carcinoma
Affected status: yes
Allele origin:
somatic
|
Institute of Medical Sciences, Banaras Hindu University
Accession: SCV001432167.1
First in ClinVar: Sep 14, 2020 Last updated: Sep 14, 2020 |
Number of individuals with the variant: 5
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001957163.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
Acute myeloid leukemia
Affected status: yes
Allele origin:
somatic
|
Dr. Afia Zoology Lab, University of Education
Accession: SCV002820082.2
First in ClinVar: Jan 21, 2023 Last updated: Feb 07, 2023 |
Ethnicity/Population group: South Asian
Geographic origin: Pakistan
|
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Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
unknown
|
Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV000692094.1
First in ClinVar: Feb 19, 2018 Last updated: Feb 19, 2018 |
|
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Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001905760.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021 |
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Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001928733.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021 |
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Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001974193.1 First in ClinVar: Oct 08, 2021 Last updated: Oct 08, 2021 |
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not provided
(Sep 19, 2013)
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no classification provided
Method: reference population
|
AllHighlyPenetrant
Affected status: unknown
Allele origin:
germline
|
ITMI
Accession: SCV000086398.1
First in ClinVar: Jun 09, 2014 Last updated: Jun 09, 2014
Comment:
Please see associated publication for description of ethnicities
|
Observation 1:
Ethnicity/Population group: Whole_cohort
Observation 2:
Ethnicity/Population group: African
Observation 3:
Ethnicity/Population group: African_European
Observation 4:
Ethnicity/Population group: Central_Asian
Observation 5:
Ethnicity/Population group: East_Asian
Observation 6:
Ethnicity/Population group: European
Observation 7:
Ethnicity/Population group: Hispanic
|
|
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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. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
Familial history and prevalence of BRCA1, BRCA2 and TP53 pathogenic variants in HBOC Brazilian patients from a public healthcare service. | Matta BP | Scientific reports | 2022 | PMID: 36329109 |
ACMG clinical laboratory standards for next-generation sequencing. | Rehm HL | Genetics in medicine : official journal of the American College of Medical Genetics | 2013 | PMID: 23887774 |
Association of MDM2 SNP309 and TP53 Arg72Pro polymorphisms with risk of endometrial cancer. | Yoneda T | Oncology reports | 2013 | PMID: 23624782 |
Polymorphisms in TP53 and MDM2 contribute to higher risk of colorectal cancer in Chinese population: a hospital-based, case-control study. | Zhang Y | Molecular biology reports | 2012 | PMID: 22744426 |
Individual and combined effects of MDM2 SNP309 and TP53 Arg72Pro on breast cancer risk: an updated meta-analysis. | Cheng H | Molecular biology reports | 2012 | PMID: 22729912 |
Is there a biological plausability for p53 codon 72 polymorphism influence on cervical cancer development? | Sousa H | Acta medica portuguesa | 2011 | PMID: 21672450 |
MDM2 SNP309, gene-gene interaction, and tumor susceptibility: an updated meta-analysis. | Wan Y | BMC cancer | 2011 | PMID: 21619694 |
Effects of MDM2, MDM4 and TP53 codon 72 polymorphisms on cancer risk in a cohort study of carriers of TP53 germline mutations. | Fang S | PloS one | 2010 | PMID: 20520810 |
Accelerated decline in lung function in cigarette smokers is associated with TP53/MDM2 polymorphisms. | Hancox RJ | Human genetics | 2009 | PMID: 19521721 |
Interaction of P53 Arg72Pro and MDM2 T309G polymorphisms and their associations with risk of gastric cardia cancer. | Yang M | Carcinogenesis | 2007 | PMID: 17638920 |
Association of the TP53 codon 72 polymorphism with colorectal cancer in a Chinese population. | Zhu ZZ | Japanese journal of clinical oncology | 2007 | PMID: 17599946 |
Tumor suppressor p53 Arg72Pro polymorphism and longevity, cancer survival, and risk of cancer in the general population. | Ørsted DD | The Journal of experimental medicine | 2007 | PMID: 17535973 |
iASPP preferentially binds p53 proline-rich region and modulates apoptotic function of codon 72-polymorphic p53. | Bergamaschi D | Nature genetics | 2006 | PMID: 16964264 |
Impact of the MDM2 SNP309 and p53 Arg72Pro polymorphism on age of tumour onset in Li-Fraumeni syndrome. | Bougeard G | Journal of medical genetics | 2006 | PMID: 16258005 |
The p53 codon 72 variation is associated with the age of onset of hereditary non-polyposis colorectal cancer (HNPCC). | Krüger S | Journal of medical genetics | 2005 | PMID: 16199549 |
p53 polymorphism and age of onset of hereditary nonpolyposis colorectal cancer in a Caucasian population. | Jones JS | Clinical cancer research : an official journal of the American Association for Cancer Research | 2004 | PMID: 15355915 |
The codon 72 polymorphic variants of p53 have markedly different apoptotic potential. | Dumont P | Nature genetics | 2003 | PMID: 12567188 |
Role of TP53 P72R polymorphism in human papillomavirus associated premalignant laryngeal neoplasm. | Aaltonen LM | Journal of medical genetics | 2001 | PMID: 11403041 |
A common polymorphism acts as an intragenic modifier of mutant p53 behaviour. | Marin MC | Nature genetics | 2000 | PMID: 10802655 |
Two polymorphic variants of wild-type p53 differ biochemically and biologically. | Thomas M | Molecular and cellular biology | 1999 | PMID: 9891044 |
Role of a p53 polymorphism in the development of human papillomavirus-associated cancer. | Storey A | Nature | 1998 | PMID: 9607760 |
WAF1, a potential mediator of p53 tumor suppression. | el-Deiry WS | Cell | 1993 | PMID: 8242752 |
Characterization of a frequent polymorphism in the coding sequence of the Tp53 gene in colonic cancer patients and a control population. | Olschwang S | Human genetics | 1991 | PMID: 1999338 |
Codon 72 polymorphism of the TP53 gene. | Ara S | Nucleic acids research | 1990 | PMID: 1975675 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=TP53 | - | - | - | - |
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Conditions - Somatic
Tumor type
Help
The tumor type for this variant-condition (RCV) record in ClinVar. |
Clinical impact (# of submissions)
Help
The aggregate somatic clinical impact for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to the aggregate somatic clinical impact is shown in parentheses. The corresponding review status for the RCV record is indicated by stars. Read our rules for calculating the review status. |
Oncogenicity
Help
The aggregate oncogenicity classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to the aggregate oncogenicity classification is shown in parentheses. The corresponding review status for the RCV record is indicated by stars. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the tumor type. |
Variation/condition record
Help
The most recent date that a submitter evaluated this variant for the tumor type. |
---|---|---|---|---|
Benign
criteria provided, single submitter
|
Jul 31, 2024 | RCV004668715.1 |
Submissions - Somatic
Oncogenicity
Help
The submitted oncogenicity 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) |
Tumor type
Help
The tumor type 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 somatic clinical impact, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Benign
(Jul 31, 2024)
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criteria provided, single submitter
Method: clinical testing
|
Neoplasm
Affected status: unknown
Allele origin:
somatic
|
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV005094471.1
First In ClinVar: Aug 11, 2024 Last updated: Aug 11, 2024 |
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Citations for somatic classification of this variant
HelpThere are no citations for somatic 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 rs1042522 ...
HelpRecord last updated Dec 15, 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.