NM_000546.5(TP53):c.145G>C (p.Asp49His) AND not specified

Clinical significance:Uncertain significance (Last evaluated: Mar 14, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001192616.1

Allele description [Variation Report for NM_000546.5(TP53):c.145G>C (p.Asp49His)]

NM_000546.5(TP53):c.145G>C (p.Asp49His)

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.145G>C (p.Asp49His)
HGVS:
  • NC_000017.11:g.7676224C>G
  • NG_017013.2:g.16327G>C
  • NM_000546.5:c.145G>C
  • NM_001126112.2:c.145G>C
  • NM_001126113.2:c.145G>C
  • NM_001126114.2:c.145G>C
  • NM_001126118.1:c.28G>C
  • NM_001276695.2:c.28G>C
  • NM_001276696.2:c.28G>C
  • NM_001276760.2:c.28G>C
  • NM_001276761.2:c.28G>C
  • NP_000537.3:p.Asp49His
  • NP_001119584.1:p.Asp49His
  • NP_001119585.1:p.Asp49His
  • NP_001119586.1:p.Asp49His
  • NP_001119590.1:p.Asp10His
  • NP_001263624.1:p.Asp10His
  • NP_001263625.1:p.Asp10His
  • NP_001263689.1:p.Asp10His
  • NP_001263690.1:p.Asp10His
  • LRG_321t1:c.145G>C
  • LRG_321t2:c.145G>C
  • LRG_321t3:c.145G>C
  • LRG_321t4:c.145G>C
  • LRG_321t8:c.28G>C
  • LRG_321:g.16327G>C
  • LRG_321:p.Asp49His
  • LRG_321p1:p.Asp49His
  • LRG_321p3:p.Asp49His
  • LRG_321p4:p.Asp49His
  • LRG_321p8:p.Asp10His
  • NC_000017.10:g.7579542C>G
  • NM_000546.4:c.145G>C
  • NM_001126112.2(TP53):c.145G>C
  • P04637:p.Asp49His
  • p.D49H
Protein change:
D10H
Links:
UniProtKB: P04637#VAR_044571; dbSNP: rs587780728
NCBI 1000 Genomes Browser:
rs587780728
Molecular consequence:
  • NM_000546.5:c.145G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126112.2:c.145G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126113.2:c.145G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126114.2:c.145G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126118.1:c.28G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276695.2:c.28G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276696.2:c.28G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276760.2:c.28G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276761.2:c.28G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001360862Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Uncertain significance
(Mar 14, 2019)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

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

Citations

PubMed

Germline variants in pancreatic cancer patients with a personal or family history of cancer fulfilling the revised Bethesda guidelines.

Ohmoto A, Morizane C, Kubo E, Takai E, Hosoi H, Sakamoto Y, Kondo S, Ueno H, Shimada K, Yachida S, Okusaka T.

J Gastroenterol. 2018 Oct;53(10):1159-1167. doi: 10.1007/s00535-018-1466-y. Epub 2018 Apr 17.

PubMed [citation]
PMID:
29667044

Mutant p53 in bone marrow stromal cells increases VEGF expression and supports leukemia cell growth.

Narendran A, Ganjavi H, Morson N, Connor A, Barlow JW, Keystone E, Malkin D, Freedman MH.

Exp Hematol. 2003 Aug;31(8):693-701.

PubMed [citation]
PMID:
12901974
See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001360862.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

Variant summary: TP53 c.145G>C (p.Asp49His) results in a non-conservative amino acid change located in the transactivation domain 2 of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8.1e-06 in 246194 control chromosomes (gnomad). This variant has been reported in the literature in individuals affected with Li-Fraumeni Syndrome and other cancers (Yamaguchi_2016, Yamazaki_2018, Ohmoto_2018). These reports do not provide unequivocal conclusions about association of the variant with Li-Fraumeni Syndrome. At least one publication reports experimental evidence evaluating an impact on protein function (Narendran_2003). The transfection experiment demonstrated the ability of p.Asp49His to increase the expression of VEGF. However, the association between this effect to Li-Fraumeni Syndrome is not clear. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS.

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

Last Updated: Jun 23, 2021

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