NM_000546.6(TP53):c.45del (p.Gln16fs) AND Li-Fraumeni syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 14, 2017
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:: RCV000633337.5

Allele description [Variation Report for NM_000546.6(TP53):c.45del (p.Gln16fs)]

NM_000546.6(TP53):c.45del (p.Gln16fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

17p13.1

Genomic location:

Preferred name:

NM_000546.6(TP53):c.45del (p.Gln16fs)

HGVS:

NC_000017.11:g.7676550del
NG_017013.2:g.16001del
NM_000546.6:c.45delMANE SELECT
NM_001126112.3:c.45del
NM_001126113.3:c.45del
NM_001126114.3:c.45del
NM_001126118.2:c.-190del
NM_001276695.3:c.-73del
NM_001276696.3:c.-73del
NM_001276760.3:c.-73del
NM_001276761.3:c.-73del
NP_000537.3:p.Gln16fs
NP_001119584.1:p.Gln16fs
NP_001119585.1:p.Gln16fs
NP_001119586.1:p.Gln16fs
LRG_321:g.16001del
NC_000017.10:g.7579868del
NC_000017.10:g.7579868delA
NM_000546.4:c.45delT
NM_000546.5:c.45delT

Protein change:

Q16fs

Links:

dbSNP: rs1555526997

NCBI 1000 Genomes Browser:

rs1555526997

Molecular consequence:

NM_001126118.2:c.-190del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276695.3:c.-73del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276696.3:c.-73del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276760.3:c.-73del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276761.3:c.-73del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000546.6:c.45del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001126112.3:c.45del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001126113.3:c.45del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001126114.3:c.45del - 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

Recent activity

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Fraxinus baroniana, whole genome shotgun sequencing project
Fraxinus baroniana, whole genome shotgun sequencing project
gi|1858415227|emb|CAIGRO000000000.1 RO010000000

Nucleotide
Fraxinus angustifolia subsp. angustifolia, whole genome shotgun sequencing proje...
Fraxinus angustifolia subsp. angustifolia, whole genome shotgun sequencing project
gi|1831504816|emb|CADEPF000000000.1 PF010000000

Nucleotide
PREDICTED: Mus musculus dolichyl pyrophosphate phosphatase 1 (Dolpp1), transcrip...
PREDICTED: Mus musculus dolichyl pyrophosphate phosphatase 1 (Dolpp1), transcript variant X2, mRNA
gi|1907142240|ref|XM_006498207.5|

Nucleotide
Mus musculus dolichyl pyrophosphate phosphatase 1 (Dolpp1), transcript variant 2...
Mus musculus dolichyl pyrophosphate phosphatase 1 (Dolpp1), transcript variant 2, mRNA
gi|2173616051|ref|NM_001290508.2|

Nucleotide
FRAX01
FRAX01

biosample

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000754559	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 14, 2017)	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

SCV000754559

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 14, 2017)

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, SCV000754559.4

#	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. Loss-of-function variants in TP53 are known to be pathogenic (PMID: 20522432). This variant has not been reported in the literature in individuals with TP53-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gln16Argfs*28) in the TP53 gene. It is expected to result in an absent or disrupted protein product.

#	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: Nov 10, 2024

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