NM_000546.6(TP53):c.636del (p.Arg213fs) AND Li-Fraumeni syndrome 1

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Sep 4, 2020
Review status:: 3 stars out of maximum of 4 stars
reviewed by expert panel

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:: RCV001527089.4

Allele description [Variation Report for NM_000546.6(TP53):c.636del (p.Arg213fs)]

NM_000546.6(TP53):c.636del (p.Arg213fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

17p13.1

Genomic location:

Preferred name:

NM_000546.6(TP53):c.636del (p.Arg213fs)

HGVS:

NC_000017.11:g.7674898del
NG_017013.2:g.17656del
NM_000546.6:c.636delMANE SELECT
NM_001126112.3:c.636del
NM_001126113.3:c.636del
NM_001126114.3:c.636del
NM_001126115.2:c.240del
NM_001126116.2:c.240del
NM_001126117.2:c.240del
NM_001126118.2:c.519del
NM_001276695.3:c.519del
NM_001276696.3:c.519del
NM_001276697.3:c.159del
NM_001276698.3:c.159del
NM_001276699.3:c.159del
NM_001276760.3:c.519del
NM_001276761.3:c.519del
NP_000537.3:p.Arg213fs
NP_001119584.1:p.Arg213fs
NP_001119585.1:p.Arg213fs
NP_001119586.1:p.Arg213fs
NP_001119587.1:p.Arg81fs
NP_001119588.1:p.Arg81fs
NP_001119589.1:p.Arg81fs
NP_001119590.1:p.Arg174fs
NP_001263624.1:p.Arg174fs
NP_001263625.1:p.Arg174fs
NP_001263626.1:p.Arg54fs
NP_001263627.1:p.Arg54fs
NP_001263628.1:p.Arg54fs
NP_001263689.1:p.Arg174fs
NP_001263690.1:p.Arg174fs
LRG_321t2:c.636del
LRG_321:g.17656del
NC_000017.10:g.7578213del
NC_000017.10:g.7578213delA
NC_000017.10:g.7578216del
NM_000546.4:c.636delT
NM_001126112.2(TP53):c.636del
p.Arg213fs

Protein change:

R174fs

Links:

dbSNP: rs864309495

NCBI 1000 Genomes Browser:

rs864309495

Molecular consequence:

NM_000546.6:c.636del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001126112.3:c.636del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001126113.3:c.636del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001126114.3:c.636del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001126115.2:c.240del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001126116.2:c.240del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001126117.2:c.240del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001126118.2:c.519del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001276695.3:c.519del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001276696.3:c.519del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001276697.3:c.159del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001276698.3:c.159del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001276699.3:c.159del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001276760.3:c.519del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001276761.3:c.519del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Li-Fraumeni syndrome 1 (LFS)
Identifiers:: Gene: 553989; MedGen: C1835398; Orphanet: 524; OMIM: 151623

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001737928	ClinGen TP53 Variant Curation Expert Panel, ClinGen	reviewed by expert panel (ClinGen TP53 ACMG Specifications v1)	Pathogenic (Sep 4, 2020)	germline	curation	Citation Link,
SCV004027693	Institute of Human Genetics, University of Leipzig Medical Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jun 15, 2023)	unknown	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

SCV001737928

ClinGen TP53 Variant Curation Expert Panel, ClinGen

reviewed by expert panel

(ClinGen TP53 ACMG Specifications v1)

Pathogenic
(Sep 4, 2020)

germline

curation

Citation Link,

SCV004027693

Institute of Human Genetics, University of Leipzig Medical Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jun 15, 2023)

unknown

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	unknown	not provided	not provided	not provided	not provided	not provided	curation
not provided	unknown	yes	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 ClinGen TP53 Variant Curation Expert Panel, ClinGen, SCV001737928.1

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

Description

The p.R213fs variant is predicted to result in a premature stop codon that leads to a truncated or absent protein (PVS1). This variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). This variant has been reported in 2 probands meeting Chompret criteria (PS4_Supporting; PMID: 11370630, NIH). In summary, TP53 c.636del (p.R213fs) meets criteria to be classified as pathogenic for Li-Fraumeni syndrome. ACMG/AMP criteria applied, as specified by the TP53 Variant Curation Expert Panel: PVS1, PM2_Supporting, PS4_Supporting.

#	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 Institute of Human Genetics, University of Leipzig Medical Center, SCV004027693.1

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

Description

Criteria applied: PVS1,PS4_MOD,PM2_SUP

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

Last Updated: Sep 29, 2024

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