NM_000546.6(TP53):c.482_487del (p.Ala161_Tyr163delinsAsp) AND Li-Fraumeni syndrome

Clinical significance:Uncertain significance (Last evaluated: Feb 26, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001361575.1

Allele description [Variation Report for NM_000546.6(TP53):c.482_487del (p.Ala161_Tyr163delinsAsp)]

NM_000546.6(TP53):c.482_487del (p.Ala161_Tyr163delinsAsp)

Gene:
TP53:tumor protein p53 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
17p13.1
Genomic location:
Preferred name:
NM_000546.6(TP53):c.482_487del (p.Ala161_Tyr163delinsAsp)
HGVS:
  • NC_000017.11:g.7675125_7675130del
  • NG_017013.2:g.17421_17426del
  • NM_000546.6:c.482_487delMANE SELECT
  • NM_001126112.2:c.482_487del
  • NM_001126113.2:c.482_487del
  • NM_001126114.2:c.482_487del
  • NM_001126115.1:c.86_91del
  • NM_001126116.1:c.86_91del
  • NM_001126117.1:c.86_91del
  • NM_001126118.1:c.365_370del
  • NM_001276695.2:c.365_370del
  • NM_001276696.2:c.365_370del
  • NM_001276697.2:c.5_10del
  • NM_001276698.2:c.5_10del
  • NM_001276699.2:c.5_10del
  • NM_001276760.2:c.365_370del
  • NM_001276761.2:c.365_370del
  • NP_000537.3:p.Ala161_Tyr163delinsAsp
  • NP_001119584.1:p.Ala161_Tyr163delinsAsp
  • NP_001119585.1:p.Ala161_Tyr163delinsAsp
  • NP_001119586.1:p.Ala161_Tyr163delinsAsp
  • NP_001119587.1:p.Ala29_Tyr31delinsAsp
  • NP_001119588.1:p.Ala29_Tyr31delinsAsp
  • NP_001119589.1:p.Ala29_Tyr31delinsAsp
  • NP_001119590.1:p.Ala122_Tyr124delinsAsp
  • NP_001263624.1:p.Ala122_Tyr124delinsAsp
  • NP_001263625.1:p.Ala122_Tyr124delinsAsp
  • NP_001263626.1:p.Ala2_Tyr4delinsAsp
  • NP_001263627.1:p.Ala2_Tyr4delinsAsp
  • NP_001263628.1:p.Ala2_Tyr4delinsAsp
  • NP_001263689.1:p.Ala122_Tyr124delinsAsp
  • NP_001263690.1:p.Ala122_Tyr124delinsAsp
  • LRG_321t1:c.482_487del
  • LRG_321t2:c.482_487del
  • LRG_321t3:c.482_487del
  • LRG_321t4:c.482_487del
  • LRG_321t5:c.86_91del
  • LRG_321t6:c.86_91del
  • LRG_321t7:c.86_91del
  • LRG_321t8:c.365_370del
  • LRG_321:g.17421_17426del
  • LRG_321:p.Ala161_Tyr163delinsAsp
  • LRG_321p3:p.Ala161_Tyr163delinsAsp
  • LRG_321p4:p.Ala161_Tyr163delinsAsp
  • LRG_321p5:p.Ala29_Tyr31delinsAsp
  • LRG_321p6:p.Ala29_Tyr31delinsAsp
  • LRG_321p7:p.Ala29_Tyr31delinsAsp
  • LRG_321p8:p.Ala122_Tyr124delinsAsp
  • NC_000017.10:g.7578443_7578448del
  • NM_000546.5:c.482_487del
Links:
Molecular consequence:
  • NM_000546.6:c.482_487del - inframe_indel - [Sequence Ontology: SO:0001820]
  • NM_001126112.2:c.482_487del - inframe_indel - [Sequence Ontology: SO:0001820]
  • NM_001126113.2:c.482_487del - inframe_indel - [Sequence Ontology: SO:0001820]
  • NM_001126114.2:c.482_487del - inframe_indel - [Sequence Ontology: SO:0001820]
  • NM_001126115.1:c.86_91del - inframe_indel - [Sequence Ontology: SO:0001820]
  • NM_001126116.1:c.86_91del - inframe_indel - [Sequence Ontology: SO:0001820]
  • NM_001126117.1:c.86_91del - inframe_indel - [Sequence Ontology: SO:0001820]
  • NM_001126118.1:c.365_370del - inframe_indel - [Sequence Ontology: SO:0001820]
  • NM_001276695.2:c.365_370del - inframe_indel - [Sequence Ontology: SO:0001820]
  • NM_001276696.2:c.365_370del - inframe_indel - [Sequence Ontology: SO:0001820]
  • NM_001276697.2:c.5_10del - inframe_indel - [Sequence Ontology: SO:0001820]
  • NM_001276698.2:c.5_10del - inframe_indel - [Sequence Ontology: SO:0001820]
  • NM_001276699.2:c.5_10del - inframe_indel - [Sequence Ontology: SO:0001820]
  • NM_001276760.2:c.365_370del - inframe_indel - [Sequence Ontology: SO:0001820]
  • NM_001276761.2:c.365_370del - 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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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001557553Invitaecriteria provided, single submitter
Uncertain significance
(Feb 26, 2020)
germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Germline mutations of the p53 tumor suppressor gene in children with osteosarcoma.

McIntyre JF, Smith-Sorensen B, Friend SH, Kassell J, Borresen AL, Yan YX, Russo C, Sato J, Barbier N, Miser J, et al.

J Clin Oncol. 1994 May;12(5):925-30.

PubMed [citation]
PMID:
8164043

Excessive genomic DNA copy number variation in the Li-Fraumeni cancer predisposition syndrome.

Shlien A, Tabori U, Marshall CR, Pienkowska M, Feuk L, Novokmet A, Nanda S, Druker H, Scherer SW, Malkin D.

Proc Natl Acad Sci U S A. 2008 Aug 12;105(32):11264-9. doi: 10.1073/pnas.0802970105. Epub 2008 Aug 6.

PubMed [citation]
PMID:
18685109
PMCID:
PMC2516272
See all PubMed Citations (6)

Details of each submission

From Invitae, SCV001557553.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

This variant, c.482_487del, results in the deletion of 2 amino acid(s) of the TP53 protein (p.Ala161_Tyr163delinsAsp), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of Li-Fraumeni syndrome (Invitae). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant disrupts the p.Tyr163 amino acid residue in TP53. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 8164043, 18685109, 19556618, 12826609, 16861262). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Apr 18, 2021

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