NM_000546.6(TP53):c.715A>G (p.Asn239Asp) AND Malignant tumor of breast

Germline classification:: Likely pathogenic (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:: RCV001355898.2

Allele description [Variation Report for NM_000546.6(TP53):c.715A>G (p.Asn239Asp)]

NM_000546.6(TP53):c.715A>G (p.Asn239Asp)

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.715A>G (p.Asn239Asp)

HGVS:

NC_000017.11:g.7674248T>C
NG_017013.2:g.18303A>G
NM_000546.6:c.715A>GMANE SELECT
NM_001126112.3:c.715A>G
NM_001126113.3:c.715A>G
NM_001126114.3:c.715A>G
NM_001126115.2:c.319A>G
NM_001126116.2:c.319A>G
NM_001126117.2:c.319A>G
NM_001126118.2:c.598A>G
NM_001276695.3:c.598A>G
NM_001276696.3:c.598A>G
NM_001276697.3:c.238A>G
NM_001276698.3:c.238A>G
NM_001276699.3:c.238A>G
NM_001276760.3:c.598A>G
NM_001276761.3:c.598A>G
NP_000537.3:p.Asn239Asp
NP_000537.3:p.Asn239Asp
NP_001119584.1:p.Asn239Asp
NP_001119585.1:p.Asn239Asp
NP_001119586.1:p.Asn239Asp
NP_001119587.1:p.Asn107Asp
NP_001119588.1:p.Asn107Asp
NP_001119589.1:p.Asn107Asp
NP_001119590.1:p.Asn200Asp
NP_001263624.1:p.Asn200Asp
NP_001263625.1:p.Asn200Asp
NP_001263626.1:p.Asn80Asp
NP_001263627.1:p.Asn80Asp
NP_001263628.1:p.Asn80Asp
NP_001263689.1:p.Asn200Asp
NP_001263690.1:p.Asn200Asp
LRG_321t1:c.715A>G
LRG_321:g.18303A>G
LRG_321p1:p.Asn239Asp
NC_000017.10:g.7577566T>C
NM_000546.4:c.715A>G
NM_000546.5:c.715A>G
P04637:p.Asn239Asp

Protein change:

N107D

Links:

UniProtKB: P04637#VAR_045204; dbSNP: rs876660807

NCBI 1000 Genomes Browser:

rs876660807

Molecular consequence:

NM_000546.6:c.715A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.715A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.715A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.715A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.319A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126116.2:c.319A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126117.2:c.319A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.598A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.598A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.598A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276697.3:c.238A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276698.3:c.238A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276699.3:c.238A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.598A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.598A>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Malignant tumor of breast
Synonyms:: Malignant breast neoplasm; Cancer breast
Identifiers:: MONDO: MONDO:0007254; MedGen: C0006142

Recent activity

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ELKS/Rab6-interacting/CAST family member 1 isoform 1 [Mus musculus]
ELKS/Rab6-interacting/CAST family member 1 isoform 1 [Mus musculus]
gi|120300971|ref|NP_444434.2|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001550915	Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR) See additional submitters Franklin by Genoox	no assertion criteria provided	Likely pathogenic	unknown	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001550915

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

See additional submitters

no assertion criteria provided

Likely pathogenic

unknown

clinical testing

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	yes	1	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV001550915.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	not provided

Description

The TP53 p.Asn239Asp variant was identified in 2 of 474 proband chromosomes (frequency: 0.004) from individuals or families with myelodysplastic syndrome or lung cancer (Belickova 2016, Fouquet 2004). The variant was also identified in dbSNP (ID: rs876660807) as "With Likely pathogenic allele", ClinVar (classified as likely pathogenic by Ambry Genetics and as uncertain significance by Invitae). The variant was not identified in LOVD 3.0 or UMD-LSDB. The variant was not identified in the following control databases: the Exome Aggregation Consortium (August 8th 2016) or the Genome Aggregation Database (Feb 27, 2017). The p.Asn239 residue is conserved across mammals and other organisms, and four out of four computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest that the variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. Functional assays in yeast showed that this variant eliminates the transactivation activity of p53 (Flaman 1998; Jordan 2010). 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 pathogenic role for this variant. This variant is classified as likely pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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