NM_000546.6(TP53):c.785G>T (p.Gly262Val) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jun 18, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000492458.5

Allele description [Variation Report for NM_000546.6(TP53):c.785G>T (p.Gly262Val)]

NM_000546.6(TP53):c.785G>T (p.Gly262Val)

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.785G>T (p.Gly262Val)

HGVS:

NC_000017.11:g.7673835C>A
NG_017013.2:g.18716G>T
NM_000546.6:c.785G>TMANE SELECT
NM_001126112.3:c.785G>T
NM_001126113.3:c.785G>T
NM_001126114.3:c.785G>T
NM_001126115.2:c.389G>T
NM_001126116.2:c.389G>T
NM_001126117.2:c.389G>T
NM_001126118.2:c.668G>T
NM_001276695.3:c.668G>T
NM_001276696.3:c.668G>T
NM_001276697.3:c.308G>T
NM_001276698.3:c.308G>T
NM_001276699.3:c.308G>T
NM_001276760.3:c.668G>T
NM_001276761.3:c.668G>T
NP_000537.3:p.Gly262Val
NP_000537.3:p.Gly262Val
NP_001119584.1:p.Gly262Val
NP_001119585.1:p.Gly262Val
NP_001119586.1:p.Gly262Val
NP_001119587.1:p.Gly130Val
NP_001119588.1:p.Gly130Val
NP_001119589.1:p.Gly130Val
NP_001119590.1:p.Gly223Val
NP_001263624.1:p.Gly223Val
NP_001263625.1:p.Gly223Val
NP_001263626.1:p.Gly103Val
NP_001263627.1:p.Gly103Val
NP_001263628.1:p.Gly103Val
NP_001263689.1:p.Gly223Val
NP_001263690.1:p.Gly223Val
LRG_321t1:c.785G>T
LRG_321:g.18716G>T
LRG_321p1:p.Gly262Val
NC_000017.10:g.7577153C>A
NM_000546.4:c.785G>T
NM_000546.5:c.785G>T

Protein change:

G103V

Links:

dbSNP: rs1131691025

NCBI 1000 Genomes Browser:

rs1131691025

Molecular consequence:

NM_000546.6:c.785G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.785G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.785G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.785G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.389G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126116.2:c.389G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126117.2:c.389G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.668G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.668G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.668G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276697.3:c.308G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276698.3:c.308G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276699.3:c.308G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.668G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.668G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

Recent activity

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3830403N01Rik RIKEN cDNA 3830403N01 gene [Mus musculus]
3830403N01Rik RIKEN cDNA 3830403N01 gene [Mus musculus]
Gene ID:76852

Gene
NAC066 NAC domain protein 66 [Arabidopsis thaliana]
NAC066 NAC domain protein 66 [Arabidopsis thaliana]
Gene ID:825364

Gene
825364[uid] AND (alive[prop]) (1)
Gene
CBXT5826.b1 NICHD_XGC_trop_25 Xenopus tropicalis cDNA clone IMAGE:8887819 5', mR...
CBXT5826.b1 NICHD_XGC_trop_25 Xenopus tropicalis cDNA clone IMAGE:8887819 5', mRNA sequence
gi|133811201|gnl|dbEST|45240808|gb| 848.1|

Nucleotide
AGENCOURT_15065561 NICHD_XGC_Emb8 Xenopus tropicalis cDNA clone IMAGE:6982221 3'...
AGENCOURT_15065561 NICHD_XGC_Emb8 Xenopus tropicalis cDNA clone IMAGE:6982221 3', mRNA sequence
gi|33426538|gnl|dbEST|19439676|gb|C 34.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000581135	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Dec 4, 2015)	germline	clinical testing	Citation Link,
SCV002581997	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jun 18, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000581135

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Dec 4, 2015)

germline

clinical testing

Citation Link,

SCV002581997

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jun 18, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Ambry Genetics, SCV000581135.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The p.G262V variant (also known as c.785G>T), located in coding exon 7 of the TP53 gene, results from a G to T substitution at nucleotide position 785. The glycine at codon 262 is replaced by valine, an amino acid with dissimilar properties. This variant is in the DNA binding domain of the TP53 protein and is reported to have loss of transactivation capacity in yeast based assays (IARC TP53 database; Kato S et al. Proc Natl Acad Sci USA. 2003 Jul 8;100(14):8424-9).This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6502 samples (13004 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.0005% (greater than 200000 alleles tested) in our clinical cohort. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.

#	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

From Genome-Nilou Lab, SCV002581997.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 13, 2024

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