NM_000546.6(TP53):c.482_487del (p.Ala161_Tyr163delinsAsp) AND Li-Fraumeni syndrome 1

Clinical significance:Uncertain significance (Last evaluated: Feb 22, 2021)

Review status:3 stars out of maximum of 4 stars

reviewed by expert panel

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV001250514.2

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 1 (LFS)
Synonyms:
Li-Fraumeni syndrome 3
Identifiers:
Gene: 553989; MONDO: MONDO:0007903; MedGen: C1835398; Orphanet: 524; OMIM: 151623

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001425306Johns Hopkins Genomics, Johns Hopkins Universitycriteria provided, single submitter
Likely pathogenic
(Mar 6, 2020)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV001481785ClinGen TP53 Variant Curation Expert Panel,ClinGenreviewed by expert panel
Uncertain significance
(Feb 22, 2021)
germlinecuration

Citation Link

Summary from all submissions

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

Citations

PubMed

The functional domains in p53 family proteins exhibit both common and distinct properties.

Harms KL, Chen X.

Cell Death Differ. 2006 Jun;13(6):890-7. Review. No abstract available.

PubMed [citation]
PMID:
16543939

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Johns Hopkins Genomics, Johns Hopkins University, SCV001425306.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From ClinGen TP53 Variant Curation Expert Panel,ClinGen, SCV001481785.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

This variant has been reported in 1 proband meeting Classic LFS criteria (PS4_Supporting; internal clinical contributor). This variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). There are 2 TP53 pathogenic variants (p.Y163C, p.A161D) previously reported at this codon (PM5; ClinVar ID 127814, 422295). In summary, the clinical significance of TP53 c.482_487del (p.Ala161_Tyr163delinsAsp) is uncertain for Li-Fraumeni syndrome. ACMG/AMP criteria applied, as specified by the TP53 Variant Curation Expert Panel: PM5, PM2_Supporting, PS4_Supporting.

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

Last Updated: Apr 18, 2021

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