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NM_000546.6(TP53):c.892G>A (p.Glu298Lys) AND Carcinoma of colon

Germline classification:
Uncertain significance (1 submission)
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV001355706.3

Allele description [Variation Report for NM_000546.6(TP53):c.892G>A (p.Glu298Lys)]

NM_000546.6(TP53):c.892G>A (p.Glu298Lys)

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.892G>A (p.Glu298Lys)
HGVS:
  • NC_000017.11:g.7673728C>T
  • NG_017013.2:g.18823G>A
  • NM_000546.6:c.892G>AMANE SELECT
  • NM_001126112.3:c.892G>A
  • NM_001126113.3:c.892G>A
  • NM_001126114.3:c.892G>A
  • NM_001126115.2:c.496G>A
  • NM_001126116.2:c.496G>A
  • NM_001126117.2:c.496G>A
  • NM_001126118.2:c.775G>A
  • NM_001276695.3:c.775G>A
  • NM_001276696.3:c.775G>A
  • NM_001276697.3:c.415G>A
  • NM_001276698.3:c.415G>A
  • NM_001276699.3:c.415G>A
  • NM_001276760.3:c.775G>A
  • NM_001276761.3:c.775G>A
  • NP_000537.3:p.Glu298Lys
  • NP_000537.3:p.Glu298Lys
  • NP_001119584.1:p.Glu298Lys
  • NP_001119585.1:p.Glu298Lys
  • NP_001119586.1:p.Glu298Lys
  • NP_001119587.1:p.Glu166Lys
  • NP_001119588.1:p.Glu166Lys
  • NP_001119589.1:p.Glu166Lys
  • NP_001119590.1:p.Glu259Lys
  • NP_001263624.1:p.Glu259Lys
  • NP_001263625.1:p.Glu259Lys
  • NP_001263626.1:p.Glu139Lys
  • NP_001263627.1:p.Glu139Lys
  • NP_001263628.1:p.Glu139Lys
  • NP_001263689.1:p.Glu259Lys
  • NP_001263690.1:p.Glu259Lys
  • LRG_321t1:c.892G>A
  • LRG_321:g.18823G>A
  • LRG_321p1:p.Glu298Lys
  • NC_000017.10:g.7577046C>T
  • NM_000546.4:c.892G>A
  • NM_000546.5(TP53):c.892G>A
  • NM_000546.5:c.892G>A
  • P04637:p.Glu298Lys
  • p.E298K
Protein change:
E139K
Links:
UniProtKB: P04637#VAR_045448; dbSNP: rs201744589
NCBI 1000 Genomes Browser:
rs201744589
Molecular consequence:
  • NM_000546.6:c.892G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126112.3:c.892G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126113.3:c.892G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126114.3:c.892G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126115.2:c.496G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126116.2:c.496G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126117.2:c.496G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126118.2:c.775G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276695.3:c.775G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276696.3:c.775G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276697.3:c.415G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276698.3:c.415G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276699.3:c.415G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276760.3:c.775G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276761.3:c.775G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Carcinoma of colon (CRC)
Synonyms:
Colonic carcinoma; Colon carcinoma
Identifiers:
MONDO: MONDO:0002032; MedGen: C0699790

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001550662Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR)

See additional submitters

no assertion criteria provided
Uncertain significanceunknownclinical testing

Help

Summary from all submissions

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

Details of each submission

From Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV001550662.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The TP53 p.Glu298Lys variant has been identified in 2 of 530 proband chromosomes (frequency: 0.004) of individuals affected with leukemia (Hof 2011). The variant was also identified in the following databases: dbSNP (ID: rs201744589) as “With Uncertain significance allele”, ClinVar (reported 3x as likely benign and uncertain significance by Ambry Genetics, Invitae and Counsyl), Cosmic (2x recurrence, endometrium, haematopoietic, Sinonasal and nasal cavity tissues, as carcinoma and lymphoid neoplasm) and IARC TP53 Database (7x somatic, 1x germline). The variant was not identified in Clinvitae, LOVD 3.0, UMD TP53 Mutation Database, and Database of germline p53 mutations. The variant was identified in control databases in 3 of 246268 chromosomes at a frequency of 0.000012 (Genome Aggregation Database Feb 27, 2017). It was observed in the following populations: Latino in 2 of 33582 chromosomes (freq: 0.00006), and South Asian in 1 of 30782 chromosomes (freq: 0.00003). It was not observed in the African, Other, European Non-Finnish, Ashkenazi Jewish, East Asian, and Finnish populations. The p.Glu298Lys residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and 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. This variant is classified as a variant of uncertain significance.

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

Last Updated: Oct 20, 2024