NM_000546.6(TP53):c.868del (p.Arg290fs) AND Li-Fraumeni syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 23, 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:: RCV001999792.4

Allele description [Variation Report for NM_000546.6(TP53):c.868del (p.Arg290fs)]

NM_000546.6(TP53):c.868del (p.Arg290fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

17p13.1

Genomic location:

Preferred name:

NM_000546.6(TP53):c.868del (p.Arg290fs)

HGVS:

NC_000017.11:g.7673753del
NG_017013.2:g.18799del
NM_000546.6:c.868delMANE SELECT
NM_001126112.3:c.868del
NM_001126113.3:c.868del
NM_001126114.3:c.868del
NM_001126115.2:c.472del
NM_001126116.2:c.472del
NM_001126117.2:c.472del
NM_001126118.2:c.751del
NM_001276695.3:c.751del
NM_001276696.3:c.751del
NM_001276697.3:c.391del
NM_001276698.3:c.391del
NM_001276699.3:c.391del
NM_001276760.3:c.751del
NM_001276761.3:c.751del
NP_000537.3:p.Arg290fs
NP_001119584.1:p.Arg290fs
NP_001119585.1:p.Arg290fs
NP_001119586.1:p.Arg290fs
NP_001119587.1:p.Arg158fs
NP_001119588.1:p.Arg158fs
NP_001119589.1:p.Arg158fs
NP_001119590.1:p.Arg251fs
NP_001263624.1:p.Arg251fs
NP_001263625.1:p.Arg251fs
NP_001263626.1:p.Arg131fs
NP_001263627.1:p.Arg131fs
NP_001263628.1:p.Arg131fs
NP_001263689.1:p.Arg251fs
NP_001263690.1:p.Arg251fs
LRG_321:g.18799del
NC_000017.10:g.7577070del
NC_000017.10:g.7577071del

Protein change:

R131fs

Links:

dbSNP: rs2151014901

NCBI 1000 Genomes Browser:

rs2151014901

Molecular consequence:

NM_000546.6:c.868del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001126112.3:c.868del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001126113.3:c.868del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001126114.3:c.868del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001126115.2:c.472del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001126116.2:c.472del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001126117.2:c.472del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001126118.2:c.751del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001276695.3:c.751del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001276696.3:c.751del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001276697.3:c.391del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001276698.3:c.391del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001276699.3:c.391del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001276760.3:c.751del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001276761.3:c.751del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV002233050	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 23, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 20522432, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002233050

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 23, 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

TP53 germline mutation testing in 180 families suspected of Li-Fraumeni syndrome: mutation detection rate and relative frequency of cancers in different familial phenotypes.

Ruijs MW, Verhoef S, Rookus MA, Pruntel R, van der Hout AH, Hogervorst FB, Kluijt I, Sijmons RH, Aalfs CM, Wagner A, Ausems MG, Hoogerbrugge N, van Asperen CJ, Gomez Garcia EB, Meijers-Heijboer H, Ten Kate LP, Menko FH, van 't Veer LJ.

J Med Genet. 2010 Jun;47(6):421-8. doi: 10.1136/jmg.2009.073429.

PubMed [citation]

PMID:: 20522432

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV002233050.3

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with TP53-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Arg290Alafs*55) in the TP53 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TP53 are known to be pathogenic (PMID: 20522432).

#	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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