NM_000546.6(TP53):c.52del (p.Thr18fs) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (3 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:: RCV000213243.9

Allele description [Variation Report for NM_000546.6(TP53):c.52del (p.Thr18fs)]

NM_000546.6(TP53):c.52del (p.Thr18fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

17p13.1

Genomic location:

Preferred name:

NM_000546.6(TP53):c.52del (p.Thr18fs)

HGVS:

NC_000017.11:g.7676545del
NG_017013.2:g.16008del
NM_000546.6:c.52delMANE SELECT
NM_001126112.3:c.52del
NM_001126113.3:c.52del
NM_001126114.3:c.52del
NM_001126118.2:c.-183del
NM_001276695.3:c.-66del
NM_001276696.3:c.-66del
NM_001276760.3:c.-66del
NM_001276761.3:c.-66del
NP_000537.3:p.Thr18fs
NP_001119584.1:p.Thr18fs
NP_001119585.1:p.Thr18fs
NP_001119586.1:p.Thr18fs
LRG_321:g.16008del
NC_000017.10:g.7579863del
NM_000546.4:c.52delA
NM_000546.5:c.52delA

Protein change:

T18fs

Links:

dbSNP: rs876658627

NCBI 1000 Genomes Browser:

rs876658627

Molecular consequence:

NM_001126118.2:c.-183del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276695.3:c.-66del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276696.3:c.-66del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276760.3:c.-66del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276761.3:c.-66del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000546.6:c.52del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001126112.3:c.52del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001126113.3:c.52del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001126114.3:c.52del - frameshift variant - [Sequence Ontology: SO:0001589]

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000274136	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Mar 2, 2015)	germline	clinical testing	Citation Link,
SCV000691599	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 11, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002582629	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (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

SCV000274136

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Mar 2, 2015)

germline

clinical testing

Citation Link,

SCV000691599

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 11, 2022)

germline

clinical testing

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

SCV002582629

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(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, SCV000274136.8

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

Description

The c.52delA pathogenic mutation, located in coding exon 1 of the TP53 gene, results from a deletion of one nucleotide at nucleotide position 52, causing a translational frameshift with a predicted alternate stop codon. Since frameshifts are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294).

#	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 Color Diagnostics, LLC DBA Color Health, SCV000691599.3

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

Description

This variant deletes 1 nucleotide in exon 2 of the TP53 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, this variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of TP53 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as 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

From Genome-Nilou Lab, SCV002582629.1

#	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: May 1, 2024

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