NM_000546.6(TP53):c.945_946del (p.Gln317fs) AND Li-Fraumeni syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 23, 2020
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:: RCV001889695.3

Allele description [Variation Report for NM_000546.6(TP53):c.945_946del (p.Gln317fs)]

NM_000546.6(TP53):c.945_946del (p.Gln317fs)

Gene:

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

Variant type:

Microsatellite

Cytogenetic location:

17p13.1

Genomic location:

Preferred name:

NM_000546.6(TP53):c.945_946del (p.Gln317fs)

HGVS:

NC_000017.11:g.7673583AG[1]
NG_017013.2:g.18966TC[1]
NM_000546.4:c.945_946delTC
NM_000546.6:c.945_946delMANE SELECT
NM_001126112.3:c.945_946del
NM_001126113.3:c.945_946del
NM_001126114.3:c.945_946del
NM_001126115.2:c.549_550del
NM_001126116.2:c.549_550del
NM_001126117.2:c.549_550del
NM_001126118.2:c.828_829del
NM_001276695.3:c.828_829del
NM_001276696.3:c.828_829del
NM_001276697.3:c.468_469del
NM_001276698.3:c.468_469del
NM_001276699.3:c.468_469del
NM_001276760.3:c.828_829del
NM_001276761.3:c.828_829del
NP_000537.3:p.Gln317fs
NP_001119584.1:p.Gln317fs
NP_001119585.1:p.Gln317fs
NP_001119586.1:p.Gln317fs
NP_001119587.1:p.Gln185fs
NP_001119588.1:p.Gln185fs
NP_001119589.1:p.Gln185fs
NP_001119590.1:p.Gln278fs
NP_001263624.1:p.Gln278fs
NP_001263625.1:p.Gln278fs
NP_001263626.1:p.Gln158fs
NP_001263627.1:p.Gln158fs
NP_001263628.1:p.Gln158fs
NP_001263689.1:p.Gln278fs
NP_001263690.1:p.Gln278fs
LRG_321:g.18966TC[1]
NC_000017.10:g.7576900_7576901del
NC_000017.10:g.7576901AG[1]

Protein change:

Q158fs

Links:

dbSNP: rs2151011929

NCBI 1000 Genomes Browser:

rs2151011929

Molecular consequence:

NM_000546.6:c.945_946del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001126112.3:c.945_946del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001126113.3:c.945_946del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001126114.3:c.945_946del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001126115.2:c.549_550del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001126116.2:c.549_550del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001126117.2:c.549_550del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001126118.2:c.828_829del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001276695.3:c.828_829del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001276696.3:c.828_829del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001276697.3:c.468_469del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001276698.3:c.468_469del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001276699.3:c.468_469del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001276760.3:c.828_829del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001276761.3:c.828_829del - 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
SCV002163566	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 23, 2020)	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

SCV002163566

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 23, 2020)

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV002163566.3

#	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 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.Gln317Alafs*19) 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: May 1, 2024

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