NM_001126112.2(TP53):c.376-2dup AND not specified

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Dec 15, 2016
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:: RCV000235779.3

Allele description

NM_001126112.2(TP53):c.376-2dup

Gene:

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

Variant type:

Duplication

Cytogenetic location:

17p13.1

Genomic location:

Preferred name:

NM_001126112.2(TP53):c.376-2dup

HGVS:

NC_000017.11:g.7675238dup
NG_017013.2:g.17313dup
NM_001126112.2:c.376-2dup
NM_001126113.2:c.376-2dup
NM_001126114.2:c.376-2dup
NM_001126115.1:c.-23dup
NM_001126116.1:c.-23dup
NM_001126117.1:c.-23dup
NM_001126118.1:c.259-2dup
NM_001276695.2:c.259-2dup
NM_001276696.2:c.259-2dup
NM_001276697.2:c.-104dup
NM_001276698.2:c.-104dup
NM_001276699.2:c.-104dup
NM_001276760.2:c.259-2dup
NM_001276761.2:c.259-2dup
LRG_321t1:c.376-2dup
LRG_321t2:c.376-2dup
LRG_321t3:c.376-2dup
LRG_321t4:c.376-2dup
LRG_321t5:c.-23dup
LRG_321t6:c.-23dup
LRG_321t7:c.-23dup
LRG_321t8:c.259-2dup
LRG_321:g.17313dup
NC_000017.10:g.7578556dup
NM_000546.4:c.376-2dupA
NM_000546.5:c.376-2dupA

Links:

dbSNP: rs751253294

NCBI 1000 Genomes Browser:

rs751253294

Molecular consequence:

NM_001126115.1:c.-23dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001126116.1:c.-23dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001126117.1:c.-23dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276697.2:c.-104dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276698.2:c.-104dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276699.2:c.-104dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001126112.2:c.376-2dup - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001126113.2:c.376-2dup - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001126114.2:c.376-2dup - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001126118.1:c.259-2dup - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001276695.2:c.259-2dup - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001276696.2:c.259-2dup - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001276760.2:c.259-2dup - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001276761.2:c.259-2dup - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000293780	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Uncertain significance (Aug 29, 2016)	germline	clinical testing	Citation Link,
SCV000602270	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest pathogenicity assessment criteria)	Uncertain significance (Dec 15, 2016)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000293780

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Uncertain significance
(Aug 29, 2016)

germline

clinical testing

Citation Link,

SCV000602270

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest pathogenicity assessment criteria)

Uncertain significance
(Dec 15, 2016)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]

PMID:: 26467025
PMCID:: PMC4737317

Details of each submission

From GeneDx, SCV000293780.7

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

Description

This variant is denoted TP53 c.376-2dupA or IVS4-2dupA and consists of a duplication of one nucleotide at the -2 position in intron 4 of the T53 gene. The normal sequence, with the base that is duplicated in braces, is ctac{a}gTAC, where the capital letters are exonic and lowercase are intronic. The adenine (A) nucleotide that is duplicated is conserved across species and is part of the canonical splice acceptor site. Multiple in silico models predict this variant to cause a reduction in use of this natural splice acceptor site, and to possibly cause abnormal gene splicing. However, in the absence of RNA or functional studies, the actual effect of this variant is unknown. TP53 c.376-2dupA was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. Based on currently available information, we consider TP53 c.376-2dupA to be a variant of uncertain significance.

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

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000602270.1

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

#	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: Nov 2, 2019

ClinVar

Relating variation to medicine