NM_000546.6(TP53):c.328_339del (p.Arg110_Phe113del) AND Hereditary cancer-predisposing syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: May 15, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000131618.5

Allele description [Variation Report for NM_000546.6(TP53):c.328_339del (p.Arg110_Phe113del)]

NM_000546.6(TP53):c.328_339del (p.Arg110_Phe113del)

Gene:

TP53:tumor protein p53 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

17p13.1

Genomic location:

Preferred name:

NM_000546.6(TP53):c.328_339del (p.Arg110_Phe113del)

HGVS:

NC_000017.11:g.7676033_7676044del
NG_017013.2:g.16510_16521del
NM_000546.6:c.328_339delMANE SELECT
NM_001126112.3:c.328_339del
NM_001126113.3:c.328_339del
NM_001126114.3:c.328_339del
NM_001126118.2:c.211_222del
NM_001276695.3:c.211_222del
NM_001276696.3:c.211_222del
NM_001276760.3:c.211_222del
NM_001276761.3:c.211_222del
NP_000537.3:p.Arg110_Phe113del
NP_001119584.1:p.Arg110_Phe113del
NP_001119585.1:p.Arg110_Phe113del
NP_001119586.1:p.Arg110_Phe113del
NP_001119590.1:p.Arg71_Phe74del
NP_001263624.1:p.Arg71_Phe74del
NP_001263625.1:p.Arg71_Phe74del
NP_001263689.1:p.Arg71_Phe74del
NP_001263690.1:p.Arg71_Phe74del
LRG_321:g.16510_16521del
NC_000017.10:g.7579351_7579362del
NM_000546.4:c.328_339del12
p.R110_F113del

Links:

dbSNP: rs587782490

NCBI 1000 Genomes Browser:

rs587782490

Molecular consequence:

NM_000546.6:c.328_339del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001126112.3:c.328_339del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001126113.3:c.328_339del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001126114.3:c.328_339del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001126118.2:c.211_222del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001276695.3:c.211_222del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001276696.3:c.211_222del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001276760.3:c.211_222del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001276761.3:c.211_222del - inframe_deletion - [Sequence Ontology: SO:0001822]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000186637	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (May 15, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 21552135, 23580068, 23894400, 9667734 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000186637

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(May 15, 2023)

germline

clinical testing

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

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Gastric cancer in individuals with Li-Fraumeni syndrome.

Masciari S, Dewanwala A, Stoffel EM, Lauwers GY, Zheng H, Achatz MI, Riegert-Johnson D, Foretova L, Silva EM, Digianni L, Verselis SJ, Schneider K, Li FP, Fraumeni J, Garber JE, Syngal S.

Genet Med. 2011 Jul;13(7):651-7. doi: 10.1097/GIM.0b013e31821628b6.

PubMed [citation]

PMID:: 21552135
PMCID:: PMC3595598

Prevalence of germline TP53 mutations in HER2+ breast cancer patients.

Rath MG, Masciari S, Gelman R, Miron A, Miron P, Foley K, Richardson AL, Krop IE, Verselis SJ, Dillon DA, Garber JE.

Breast Cancer Res Treat. 2013 May;139(1):193-8. doi: 10.1007/s10549-012-2375-z. Epub 2013 Apr 12.

PubMed [citation]

PMID:: 23580068
PMCID:: PMC4280061

See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV000186637.10

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

The c.328_339del12 variant (also known as p.R110_F113del) is located in coding exon 3 of the TP53 gene. This variant results from an in-frame deletion of 12 nucleotides (CGTCTGGGCTTC) at positions 328 to 339. This results in the in-frame deletion of 4 amino acids (RLGF) at codons 110 to 113. The amino acid positions 111 and 113 are well conserved, and amino acid positions 110 and 112 are not well conserved. Yeast-based functional assays shows that missense alterations at the deleted codons result primarily in a non-functional p53 protein (Kato S et al. Proc Natl Acad Sci USA. 2003 Jul 8;100(14):8424-9). In addition, missense alterations in codon 110 have been identified a Li-Fraumeni family, and as germline alterations in a number of p53-related cancers, including early onset breast cancer and sarcoma (Mitchell G, PLoS ONE 2013 ; 8(7):e69026. Rath MG, Breast Cancer Res. Treat. 2013 May; 139(1):193-8. Masciari S, Genet. Med. 2011 Jul; 13(7):651-7. Rines RD, Carcinogenesis 1998 Jun; 19(6):979-84). Structural analysis indicates that this deletion exhibits structural perturbations to the DNA binding domain and would be pathogenic (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic.

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

Last Updated: May 1, 2024

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