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NM_000546.6(TP53):c.63C>T (p.Asp21=) AND not provided

Germline classification:
Benign (3 submissions)
Last evaluated:
Jun 20, 2023
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV000590622.9

Allele description [Variation Report for NM_000546.6(TP53):c.63C>T (p.Asp21=)]

NM_000546.6(TP53):c.63C>T (p.Asp21=)

Gene:
TP53:tumor protein p53 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17p13.1
Genomic location:
Preferred name:
NM_000546.6(TP53):c.63C>T (p.Asp21=)
HGVS:
  • NC_000017.11:g.7676532G>A
  • NG_017013.2:g.16019C>T
  • NM_000546.6:c.63C>TMANE SELECT
  • NM_001126112.3:c.63C>T
  • NM_001126113.3:c.63C>T
  • NM_001126114.3:c.63C>T
  • NM_001126118.2:c.-172C>T
  • NM_001276695.3:c.-55C>T
  • NM_001276696.3:c.-55C>T
  • NM_001276760.3:c.-55C>T
  • NM_001276761.3:c.-55C>T
  • NP_000537.3:p.Asp21=
  • NP_000537.3:p.Asp21=
  • NP_001119584.1:p.Asp21=
  • NP_001119585.1:p.Asp21=
  • NP_001119586.1:p.Asp21=
  • LRG_321t1:c.63C>T
  • LRG_321:g.16019C>T
  • LRG_321p1:p.Asp21=
  • NC_000017.10:g.7579850G>A
  • NM_000546.4:c.63C>T
  • NM_000546.5:c.63C>T
  • p.D21D
Links:
dbSNP: rs1800369
NCBI 1000 Genomes Browser:
rs1800369
Molecular consequence:
  • NM_001126118.2:c.-172C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001276695.3:c.-55C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001276696.3:c.-55C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001276760.3:c.-55C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001276761.3:c.-55C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_000546.6:c.63C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001126112.3:c.63C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001126113.3:c.63C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001126114.3:c.63C>T - synonymous variant - [Sequence Ontology: SO:0001819]
Observations:
1

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000697443Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)
Benign
(Jun 23, 2017)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

LabCorp Variant Classification Summary - May 2015.docx,

Citation Link,

SCV001134874Quest Diagnostics Nichols Institute San Juan Capistrano
criteria provided, single submitter

(Quest Diagnostics criteria)
Benign
(Jun 20, 2023)
unknownclinical testing

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

SCV001549707Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR)

See additional submitters

no assertion criteria provided
Likely benignunknownclinical testing

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownyes1not providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Frequent occurrence of gastric cancer in Asian kindreds with Li-Fraumeni syndrome.

Ariffin H, Chan AS, Oh L, Abd-Ghafar S, Ong GB, Mohamed M, Razali H, Juraida E, Teo SH, Karsa M, Shamsani J, Hainaut P.

Clin Genet. 2015 Nov;88(5):450-5. doi: 10.1111/cge.12525. Epub 2014 Nov 13.

PubMed [citation]
PMID:
25318593

High incidence of protein-truncating TP53 mutations in BRCA1-related breast cancer.

Holstege H, Joosse SA, van Oostrom CT, Nederlof PM, de Vries A, Jonkers J.

Cancer Res. 2009 Apr 15;69(8):3625-33. doi: 10.1158/0008-5472.CAN-08-3426. Epub 2009 Mar 31.

PubMed [citation]
PMID:
19336573
See all PubMed Citations (6)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000697443.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

Variant summary: The TP53 c.63C>T (p.Asp21Asp) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect ESE sites at the locus. However, these predictions have yet to be confirmed by functional studies. This variant was found in the large control database ExAC in 73 of 119254 control chromosomes (2 homozygotes), but was observed exclusively in the South Asian subpopulation at a frequency of 0.004463 (73/16356; 2 homozygotes). This frequency is about 112 times the estimated maximal expected allele frequency of a pathogenic TP53 variant (0.0000398), strongly suggesting this is likely a benign polymorphism found primarily in the populations of South Asian origin. The variant has been identified in breast cancer and lung cancer patients without evidence for pathogenicity (Holstege_Can Res_2009; Ginsburg_Fam Cancer_2009; Lee_JCMS_2010). Immunostaining studies in breast cancer tissue showed that TP53 was present in all cells analyzed, suggesting the variant does not affect expression (Holstege_Can Res_2009). Multiple clinical diagnostic laboratories/reputable databases have classified this variant with conflicting interpretations, including uncertain significance, likely benign and benign. Taken together, this variant is classified as benign.

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

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV001134874.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV001549707.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided

Description

The TP53 p.Asp21= variant was identified in 4 of 658 proband chromosomes (frequency: 0.01) from individuals or families with breast cancer (Ginsburg 2009, Holstege 2009, Lee 2010). The variant was also identified in dbSNP (ID: rs1800369) as "With other allele", ClinVar (classified as benign by Invitae, GeneDx, Integrated Genetics/Laboratory Corporation of America; as likely benign by Color Genomics, Ambry Genetics), and in IARC TP53 (2x). The variant was not identified in the COGR, or LOVD 3.0 databases. The variant was identified in control databases in 136 of 245170 chromosomes (2 homozygous) at a frequency of 0.001 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the South Asian population in 136 of 30680 chromosomes (freq: 0.004), while the variant was not observed in the African, Other, Latino, European, Ashkenazi Jewish, East Asian, and Finnish populations. The p.Asp21= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.

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

Last Updated: Nov 10, 2024