NM_000546.5(TP53):c.21T>A (p.Asp7Glu) AND Hereditary cancer-predisposing syndrome

Clinical significance:Conflicting interpretations of pathogenicity, Likely benign(1);Uncertain significance(1) (Last evaluated: Feb 16, 2021)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000128929.8

Allele description [Variation Report for NM_000546.5(TP53):c.21T>A (p.Asp7Glu)]

NM_000546.5(TP53):c.21T>A (p.Asp7Glu)

Gene:
TP53:tumor protein p53 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17p13.1
Genomic location:
Preferred name:
NM_000546.5(TP53):c.21T>A (p.Asp7Glu)
Other names:
p.D7E:GAT>GAA
HGVS:
  • NC_000017.11:g.7676574A>T
  • NG_017013.2:g.15977T>A
  • NM_000546.5:c.21T>A
  • NM_001126112.2:c.21T>A
  • NM_001126113.2:c.21T>A
  • NM_001126114.2:c.21T>A
  • NM_001126118.1:c.-214T>A
  • NM_001276695.2:c.-97T>A
  • NM_001276696.2:c.-97T>A
  • NM_001276760.2:c.-97T>A
  • NM_001276761.2:c.-97T>A
  • NP_000537.3:p.Asp7Glu
  • NP_001119584.1:p.Asp7Glu
  • NP_001119585.1:p.Asp7Glu
  • NP_001119586.1:p.Asp7Glu
  • LRG_321t1:c.21T>A
  • LRG_321t2:c.21T>A
  • LRG_321t3:c.21T>A
  • LRG_321t4:c.21T>A
  • LRG_321t8:c.-214T>A
  • LRG_321:g.15977T>A
  • LRG_321:p.Asp7Glu
  • LRG_321p1:p.Asp7Glu
  • LRG_321p3:p.Asp7Glu
  • LRG_321p4:p.Asp7Glu
  • NC_000017.10:g.7579892A>T
  • NM_000546.4:c.21T>A
  • NM_000546.5(TP53):c.21T>A
  • p.Asp7Glu
  • p.D7E
Protein change:
D7E
Links:
dbSNP: rs587781277
NCBI 1000 Genomes Browser:
rs587781277
Molecular consequence:
  • NM_001126118.1:c.-214T>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001276695.2:c.-97T>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001276696.2:c.-97T>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001276760.2:c.-97T>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001276761.2:c.-97T>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_000546.5:c.21T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126112.2:c.21T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126113.2:c.21T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126114.2:c.21T>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MedGen: C0027672

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000172800Ambry Geneticscriteria provided, single submitter
Likely benign
(Jul 24, 2017)
germlineclinical testing

Citation Link,

SCV001736275Color Health, Inccriteria provided, single submitter
Uncertain significance
(Feb 16, 2021)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing

Citations

PubMed

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 Ambry Genetics, SCV000172800.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided

Description

In silico models in agreement (benign);Other data supporting benign classification

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

From Color Health, Inc, SCV001736275.1

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

Description

This missense variant replaces aspartic acid with glutamic acid at codon 7 of the TP53 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Functional studies have shown the mutant protein to be functional in yeast transactivation assay (PMID: 12826609 and IARC database) and to lack a dominant negative effect or loss-of-function phenotype in human cell growth assay (PMID: 30224644). To our knowledge, this variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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

Last Updated: Jun 19, 2021

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