NM_000546.6(TP53):c.5A>G (p.Glu2Gly) AND Li-Fraumeni syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 25, 2021
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:: RCV001876218.4

Allele description [Variation Report for NM_000546.6(TP53):c.5A>G (p.Glu2Gly)]

NM_000546.6(TP53):c.5A>G (p.Glu2Gly)

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.5A>G (p.Glu2Gly)

HGVS:

NC_000017.11:g.7676590T>C
NG_017013.2:g.15961A>G
NM_000546.6:c.5A>GMANE SELECT
NM_001126112.3:c.5A>G
NM_001126113.3:c.5A>G
NM_001126114.3:c.5A>G
NM_001126118.2:c.-230A>G
NM_001276695.3:c.-113A>G
NM_001276696.3:c.-113A>G
NM_001276760.3:c.-113A>G
NM_001276761.3:c.-113A>G
NP_000537.3:p.Glu2Gly
NP_001119584.1:p.Glu2Gly
NP_001119585.1:p.Glu2Gly
NP_001119586.1:p.Glu2Gly
LRG_321t1:c.5A>G
LRG_321:g.15961A>G
NC_000017.10:g.7579908T>C
NC_000017.10:g.7579908T>C
NM_000546.5:c.5A>G

Protein change:

E2G

Links:

dbSNP: rs2073524631

NCBI 1000 Genomes Browser:

rs2073524631

Molecular consequence:

NM_001126118.2:c.-230A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276695.3:c.-113A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276696.3:c.-113A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276760.3:c.-113A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276761.3:c.-113A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000546.6:c.5A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.5A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.5A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.5A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Li-Fraumeni syndrome (LFS)
Synonyms:: Sarcoma family syndrome of Li and Fraumeni
Identifiers:: MONDO: MONDO:0018875; MedGen: C0085390; OMIM: PS151623

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002277562	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 25, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 12826609, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002277562

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 25, 2021)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

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

Understanding the function-structure and function-mutation relationships of p53 tumor suppressor protein by high-resolution missense mutation analysis.

Kato S, Han SY, Liu W, Otsuka K, Shibata H, Kanamaru R, Ishioka C.

Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8424-9. Epub 2003 Jun 25.

PubMed [citation]

PMID:: 12826609
PMCID:: PMC166245

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV002277562.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 2 of the TP53 protein (p.Glu2Gly). This variant has not been reported in the literature in individuals affected with TP53-related conditions. 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. Experimental studies have shown that this missense change does not substantially affect TP53 function (PMID: 12826609). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 926778).

#	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: Jun 23, 2024

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