NM_000546.6(TP53):c.643A>G (p.Ser215Gly) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 29, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV002282093.2

Allele description [Variation Report for NM_000546.6(TP53):c.643A>G (p.Ser215Gly)]

NM_000546.6(TP53):c.643A>G (p.Ser215Gly)

Gene:

TP53:tumor protein p53 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17p13.1

Genomic location:

Preferred name:

NM_000546.6(TP53):c.643A>G (p.Ser215Gly)

HGVS:

NC_000017.11:g.7674888T>C
NG_017013.2:g.17663A>G
NM_000546.6:c.643A>GMANE SELECT
NM_001126112.3:c.643A>G
NM_001126113.3:c.643A>G
NM_001126114.3:c.643A>G
NM_001126115.2:c.247A>G
NM_001126116.2:c.247A>G
NM_001126117.2:c.247A>G
NM_001126118.2:c.526A>G
NM_001276695.3:c.526A>G
NM_001276696.3:c.526A>G
NM_001276697.3:c.166A>G
NM_001276698.3:c.166A>G
NM_001276699.3:c.166A>G
NM_001276760.3:c.526A>G
NM_001276761.3:c.526A>G
NP_000537.3:p.Ser215Gly
NP_000537.3:p.Ser215Gly
NP_001119584.1:p.Ser215Gly
NP_001119585.1:p.Ser215Gly
NP_001119586.1:p.Ser215Gly
NP_001119587.1:p.Ser83Gly
NP_001119588.1:p.Ser83Gly
NP_001119589.1:p.Ser83Gly
NP_001119590.1:p.Ser176Gly
NP_001263624.1:p.Ser176Gly
NP_001263625.1:p.Ser176Gly
NP_001263626.1:p.Ser56Gly
NP_001263627.1:p.Ser56Gly
NP_001263628.1:p.Ser56Gly
NP_001263689.1:p.Ser176Gly
NP_001263690.1:p.Ser176Gly
LRG_321t1:c.643A>G
LRG_321:g.17663A>G
LRG_321p1:p.Ser215Gly
NC_000017.10:g.7578206T>C
NM_000546.4:c.643A>G
NM_000546.5:c.643A>G
P04637:p.Ser215Gly

Protein change:

S176G

Links:

UniProtKB: P04637#VAR_045092; dbSNP: rs886039484

NCBI 1000 Genomes Browser:

rs886039484

Molecular consequence:

NM_000546.6:c.643A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.643A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.643A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.643A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.247A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126116.2:c.247A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126117.2:c.247A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.526A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.526A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.526A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276697.3:c.166A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276698.3:c.166A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276699.3:c.166A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.526A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.526A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002572405	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Aug 29, 2022)	germline	clinical testing	PubMed (22) [See all records that cite these PMIDs] 17606709, 21343334, 20407015, 26230955, 21519010, 27463065, 25952993, 22186996, 27680515, 27959731, 16818505, 27895058, 30327374, 11782540, 23246812, 22915647, 26585234, 22862161, 27276561, 30216591, 29979965, 21080251 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002572405

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Aug 29, 2022)

germline

clinical testing

PubMed (22)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Transcriptional functionality of germ line p53 mutants influences cancer phenotype.

Monti P, Ciribilli Y, Jordan J, Menichini P, Umbach DM, Resnick MA, Luzzatto L, Inga A, Fronza G.

Clin Cancer Res. 2007 Jul 1;13(13):3789-95.

PubMed [citation]

PMID:: 17606709
PMCID:: PMC2128783

Dominant-negative features of mutant TP53 in germline carriers have limited impact on cancer outcomes.

Monti P, Perfumo C, Bisio A, Ciribilli Y, Menichini P, Russo D, Umbach DM, Resnick MA, Inga A, Fronza G.

Mol Cancer Res. 2011 Mar;9(3):271-9. doi: 10.1158/1541-7786.MCR-10-0496. Epub 2011 Feb 22.

PubMed [citation]

PMID:: 21343334
PMCID:: PMC3077904

See all PubMed Citations (22)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002572405.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (22)

Description

Variant summary: TP53 c.643A>G (p.Ser215Gly) results in a non-conservative amino acid change located in the p53, DNA-binding domain (IPR011615) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251466 control chromosomes (gnomAD). c.643A>G has been reported in the literature in the germline of individuals affected with Ovarian cancer (Weber-Lassalle_2018) and Gastric cancer (Chen_2011). These data do not allow any conclusion about variant significance. In cancer cell culture proliferation/survival assays, the variant was found to have reduced apoptotic activity compared to wild-type Tp53 when introduced to cancer cell lines, but had greater activity when compared to null variants (Slovackova_2012, Kotler_2018). Six ClinVar submitters have assessed the variant since 2014: four classified the variant as likely pathogenic and two as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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