NM_000546.6(TP53):c.786_796del (p.Asn263fs) AND Li-Fraumeni syndrome

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 21, 2022
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:: RCV003622561.1

Allele description

NM_000546.6(TP53):c.786_796del (p.Asn263fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

17p13.1

Genomic location:

Preferred name:

NM_000546.6(TP53):c.786_796del (p.Asn263fs)

HGVS:

NC_000017.11:g.7673827_7673837del
NG_017013.2:g.18717_18727del
NM_000546.6:c.786_796delMANE SELECT
NM_001126112.3:c.786_796del
NM_001126113.3:c.786_796del
NM_001126114.3:c.786_796del
NM_001126115.2:c.390_400del
NM_001126116.2:c.390_400del
NM_001126117.2:c.390_400del
NM_001126118.2:c.669_679del
NM_001276695.3:c.669_679del
NM_001276696.3:c.669_679del
NM_001276697.3:c.309_319del
NM_001276698.3:c.309_319del
NM_001276699.3:c.309_319del
NM_001276760.3:c.669_679del
NM_001276761.3:c.669_679del
NM_001407262.1:c.786_796del
NM_001407263.1:c.669_679del
NM_001407264.1:c.786_796del
NM_001407265.1:c.669_679del
NM_001407266.1:c.786_796del
NM_001407267.1:c.669_679del
NM_001407268.1:c.786_796del
NM_001407269.1:c.669_679del
NM_001407270.1:c.786_796del
NM_001407271.1:c.669_679del
NP_000537.3:p.Asn263Thrfs
NP_000537.3:p.Asn263fs
NP_001119584.1:p.Asn263Thrfs
NP_001119584.1:p.Asn263fs
NP_001119585.1:p.Asn263Thrfs
NP_001119585.1:p.Asn263fs
NP_001119586.1:p.Asn263Thrfs
NP_001119586.1:p.Asn263fs
NP_001119587.1:p.Asn131Thrfs
NP_001119587.1:p.Asn131fs
NP_001119588.1:p.Asn131Thrfs
NP_001119588.1:p.Asn131fs
NP_001119589.1:p.Asn131Thrfs
NP_001119589.1:p.Asn131fs
NP_001119590.1:p.Asn224Thrfs
NP_001119590.1:p.Asn224fs
NP_001263624.1:p.Asn224fs
NP_001263625.1:p.Asn224fs
NP_001263626.1:p.Asn104fs
NP_001263627.1:p.Asn104fs
NP_001263628.1:p.Asn104fs
NP_001263689.1:p.Asn224fs
NP_001263690.1:p.Asn224fs
NP_001394191.1:p.Asn263fs
NP_001394192.1:p.Asn224fs
NP_001394193.1:p.Asn263fs
NP_001394194.1:p.Asn224fs
NP_001394195.1:p.Asn263fs
NP_001394196.1:p.Asn224fs
NP_001394197.1:p.Asn263fs
NP_001394198.1:p.Asn224fs
NP_001394199.1:p.Asn263fs
NP_001394200.1:p.Asn224fs
LRG_321t1:c.783_793del
LRG_321t2:c.783_793del
LRG_321t3:c.783_793del
LRG_321t4:c.783_793del
LRG_321t5:c.387_397del
LRG_321t6:c.387_397del
LRG_321t7:c.387_397del
LRG_321t8:c.666_676del
LRG_321:g.18717_18727del
LRG_321:p.Asn263Thrfs
LRG_321p1:p.Asn263Thrfs
LRG_321p3:p.Asn263Thrfs
LRG_321p4:p.Asn263Thrfs
LRG_321p5:p.Asn131Thrfs
LRG_321p6:p.Asn131Thrfs
LRG_321p7:p.Asn131Thrfs
LRG_321p8:p.Asn224Thrfs
NC_000017.10:g.7577142_7577152del
NC_000017.10:g.7577145_7577155del
NM_000546.5:c.783_793delTGGTAATCTAC
NM_001126112.2:c.783_793delTGGTAATCTAC
NM_001126113.2:c.783_793delTGGTAATCTAC
NM_001126114.2:c.783_793delTGGTAATCTAC
NM_001126115.1:c.387_397delTGGTAATCTAC
NM_001126116.1:c.387_397delTGGTAATCTAC
NM_001126117.1:c.387_397delTGGTAATCTAC
NM_001126118.1:c.666_676delTGGTAATCTAC
NR_176326.1:n.815_825del

Protein change:

N104fs

Molecular consequence:

NM_000546.6:c.786_796del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001126112.3:c.786_796del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001126113.3:c.786_796del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001126114.3:c.786_796del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001126115.2:c.390_400del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001126116.2:c.390_400del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001126117.2:c.390_400del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001126118.2:c.669_679del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001276695.3:c.669_679del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001276696.3:c.669_679del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001276697.3:c.309_319del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001276698.3:c.309_319del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001276699.3:c.309_319del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001276760.3:c.669_679del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001276761.3:c.669_679del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407262.1:c.786_796del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407263.1:c.669_679del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407264.1:c.786_796del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407265.1:c.669_679del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407266.1:c.786_796del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407267.1:c.669_679del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407268.1:c.786_796del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407269.1:c.669_679del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407270.1:c.786_796del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407271.1:c.669_679del - frameshift variant - [Sequence Ontology: SO:0001589]
NR_176326.1:n.815_825del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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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PREDICTED: Medicago truncatula F-box protein At4g35930 (LOC11440152), transcript...
PREDICTED: Medicago truncatula F-box protein At4g35930 (LOC11440152), transcript variant X1, mRNA
gi|1995157857|ref|XM_024771796.2|

Nucleotide
AAF75765 AND 1[s_discriminator] (0)
dbGaP
up22d01.x1 NCI_CGAP_Mam2 Mus musculus cDNA clone IMAGE:2655073 3', mRNA sequence
up22d01.x1 NCI_CGAP_Mam2 Mus musculus cDNA clone IMAGE:2655073 3', mRNA sequence
gi|6558113|gnl|dbEST|3586450|gb|AW2 .1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004404801	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 21, 2022)	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

SCV004404801

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 21, 2022)

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 Invitae, SCV004404801.1

#	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 (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Asn263Thrfs*5) 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: Feb 28, 2024

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