NM_000546.6(TP53):c.652_663del (p.Val218_Glu221del) AND Li-Fraumeni syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 14, 2023
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:: RCV002843347.2

Allele description [Variation Report for NM_000546.6(TP53):c.652_663del (p.Val218_Glu221del)]

NM_000546.6(TP53):c.652_663del (p.Val218_Glu221del)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

17p13.1

Genomic location:

Preferred name:

NM_000546.6(TP53):c.652_663del (p.Val218_Glu221del)

HGVS:

NC_000017.11:g.7674869_7674880del
NG_017013.2:g.17672_17683del
NM_000546.6:c.652_663delMANE SELECT
NM_001126112.3:c.652_663del
NM_001126113.3:c.652_663del
NM_001126114.3:c.652_663del
NM_001126115.2:c.256_267del
NM_001126116.2:c.256_267del
NM_001126117.2:c.256_267del
NM_001126118.2:c.535_546del
NM_001276695.3:c.535_546del
NM_001276696.3:c.535_546del
NM_001276697.3:c.175_186del
NM_001276698.3:c.175_186del
NM_001276699.3:c.175_186del
NM_001276760.3:c.535_546del
NM_001276761.3:c.535_546del
NM_001407262.1:c.651_662delGGTGCCCTATGA
NM_001407263.1:c.534_545delGGTGCCCTATGA
NM_001407264.1:c.651_662delGGTGCCCTATGA
NM_001407265.1:c.534_545delGGTGCCCTATGA
NM_001407266.1:c.651_662delGGTGCCCTATGA
NM_001407267.1:c.534_545delGGTGCCCTATGA
NM_001407268.1:c.651_662delGGTGCCCTATGA
NM_001407269.1:c.534_545delGGTGCCCTATGA
NM_001407270.1:c.651_662delGGTGCCCTATGA
NM_001407271.1:c.534_545delGGTGCCCTATGA
NP_000537.3:p.Val218_Glu221del
NP_000537.3:p.Val218_Glu221del
NP_001119584.1:p.Val218_Glu221del
NP_001119584.1:p.Val218_Glu221del
NP_001119585.1:p.Val218_Glu221del
NP_001119585.1:p.Val218_Glu221del
NP_001119586.1:p.Val218_Glu221del
NP_001119586.1:p.Val218_Glu221del
NP_001119587.1:p.Val86_Glu89del
NP_001119587.1:p.Val86_Glu89del
NP_001119588.1:p.Val86_Glu89del
NP_001119588.1:p.Val86_Glu89del
NP_001119589.1:p.Val86_Glu89del
NP_001119589.1:p.Val86_Glu89del
NP_001119590.1:p.Val179_Glu182del
NP_001119590.1:p.Val179_Glu182del
NP_001263624.1:p.Val179_Glu182del
NP_001263625.1:p.Val179_Glu182del
NP_001263626.1:p.Val59_Glu62del
NP_001263627.1:p.Val59_Glu62del
NP_001263628.1:p.Val59_Glu62del
NP_001263689.1:p.Val179_Glu182del
NP_001263690.1:p.Val179_Glu182del
NP_001394191.1:p.Val218_Glu221del
NP_001394192.1:p.Val179_Glu182del
NP_001394193.1:p.Val218_Glu221del
NP_001394194.1:p.Val179_Glu182del
NP_001394195.1:p.Val218_Glu221del
NP_001394196.1:p.Val179_Glu182del
NP_001394197.1:p.Val218_Glu221del
NP_001394198.1:p.Val179_Glu182del
NP_001394199.1:p.Val218_Glu221del
NP_001394200.1:p.Val179_Glu182del
LRG_321t1:c.651_662del
LRG_321t2:c.651_662del
LRG_321t3:c.651_662del
LRG_321t4:c.651_662del
LRG_321t5:c.255_266del
LRG_321t6:c.255_266del
LRG_321t7:c.255_266del
LRG_321t8:c.534_545del
LRG_321:g.17672_17683del
LRG_321:p.Val218_Glu221del
LRG_321p1:p.Val218_Glu221del
LRG_321p3:p.Val218_Glu221del
LRG_321p4:p.Val218_Glu221del
LRG_321p5:p.Val86_Glu89del
LRG_321p6:p.Val86_Glu89del
LRG_321p7:p.Val86_Glu89del
LRG_321p8:p.Val179_Glu182del
NC_000017.10:g.7578186_7578197del
NC_000017.10:g.7578187_7578198del
NM_000546.5:c.651_662delGGTGCCCTATGA
NM_001126112.2:c.651_662delGGTGCCCTATGA
NM_001126113.2:c.651_662delGGTGCCCTATGA
NM_001126114.2:c.651_662delGGTGCCCTATGA
NM_001126115.1:c.255_266delGGTGCCCTATGA
NM_001126116.1:c.255_266delGGTGCCCTATGA
NM_001126117.1:c.255_266delGGTGCCCTATGA
NM_001126118.1:c.534_545delGGTGCCCTATGA

Molecular consequence:

NM_000546.6:c.652_663del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001126112.3:c.652_663del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001126113.3:c.652_663del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001126114.3:c.652_663del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001126115.2:c.256_267del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001126116.2:c.256_267del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001126117.2:c.256_267del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001126118.2:c.535_546del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001276695.3:c.535_546del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001276696.3:c.535_546del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001276697.3:c.175_186del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001276698.3:c.175_186del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001276699.3:c.175_186del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001276760.3:c.535_546del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001276761.3:c.535_546del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001407262.1:c.651_662delGGTGCCCTATGA - inframe_indel - [Sequence Ontology: SO:0001820]
NM_001407263.1:c.534_545delGGTGCCCTATGA - inframe_indel - [Sequence Ontology: SO:0001820]
NM_001407264.1:c.651_662delGGTGCCCTATGA - inframe_indel - [Sequence Ontology: SO:0001820]
NM_001407265.1:c.534_545delGGTGCCCTATGA - inframe_indel - [Sequence Ontology: SO:0001820]
NM_001407266.1:c.651_662delGGTGCCCTATGA - inframe_indel - [Sequence Ontology: SO:0001820]
NM_001407267.1:c.534_545delGGTGCCCTATGA - inframe_indel - [Sequence Ontology: SO:0001820]
NM_001407268.1:c.651_662delGGTGCCCTATGA - inframe_indel - [Sequence Ontology: SO:0001820]
NM_001407269.1:c.534_545delGGTGCCCTATGA - inframe_indel - [Sequence Ontology: SO:0001820]
NM_001407270.1:c.651_662delGGTGCCCTATGA - inframe_indel - [Sequence Ontology: SO:0001820]
NM_001407271.1:c.534_545delGGTGCCCTATGA - inframe_indel - [Sequence Ontology: SO:0001820]

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
SCV003211641	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 14, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 8118819, 10432928, 18307025, 19101993, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003211641

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 14, 2023)

germline

clinical testing

PubMed (5)
[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

Prevalence and diversity of constitutional mutations in the p53 gene among 21 Li-Fraumeni families.

Birch JM, Hartley AL, Tricker KJ, Prosser J, Condie A, Kelsey AM, Harris M, Jones PH, Binchy A, Crowther D, et al.

Cancer Res. 1994 Mar 1;54(5):1298-304.

PubMed [citation]

PMID:: 8118819

Germ-line TP53 mutations in Finnish cancer families exhibiting features of the Li-Fraumeni syndrome and negative for BRCA1 and BRCA2.

Huusko P, Castrén K, Launonen V, Soini Y, Pääkkönen K, Leisti J, Vähäkangas K, Winqvist R.

Cancer Genet Cytogenet. 1999 Jul 1;112(1):9-14.

PubMed [citation]

PMID:: 10432928

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV003211641.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This variant, c.652_663del, results in the deletion of 4 amino acid(s) of the TP53 protein (p.Val218_Glu221del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TP53-related conditions. ClinVar contains an entry for this variant (Variation ID: 2012758). This variant disrupts a region of the TP53 protein in which other variant(s) (p.Tyr220Cys) have been determined to be pathogenic (PMID: 8118819, 10432928, 18307025, 19101993). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

#	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

ClinVar

Relating variation to medicine