NM_000546.6(TP53):c.376-2A>G AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Apr 18, 2022
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:: RCV000480344.6

Allele description [Variation Report for NM_000546.6(TP53):c.376-2A>G]

NM_000546.6(TP53):c.376-2A>G

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.376-2A>G

HGVS:

NC_000017.11:g.7675238T>C
NG_017013.2:g.17313A>G
NM_000546.6:c.376-2A>GMANE SELECT
NM_001126112.3:c.376-2A>G
NM_001126113.3:c.376-2A>G
NM_001126114.3:c.376-2A>G
NM_001126115.2:c.-23A>G
NM_001126116.2:c.-23A>G
NM_001126117.2:c.-23A>G
NM_001126118.2:c.259-2A>G
NM_001276695.3:c.259-2A>G
NM_001276696.3:c.259-2A>G
NM_001276697.3:c.-104A>G
NM_001276698.3:c.-104A>G
NM_001276699.3:c.-104A>G
NM_001276760.3:c.259-2A>G
NM_001276761.3:c.259-2A>G
NM_001407262.1:c.376-2A>G
NM_001407263.1:c.259-2A>G
NM_001407264.1:c.376-2A>G
NM_001407265.1:c.259-2A>G
NM_001407266.1:c.376-2A>G
NM_001407267.1:c.259-2A>G
NM_001407268.1:c.376-2A>G
NM_001407269.1:c.259-2A>G
NM_001407270.1:c.376-2A>G
NM_001407271.1:c.259-2A>G
LRG_321t1:c.376-2A>G
LRG_321t5:c.-23A>G
LRG_321t6:c.-23A>G
LRG_321t7:c.-23A>G
LRG_321:g.17313A>G
NC_000017.10:g.7578556T>C
NM_000546.4:c.376-2A>G
NM_000546.5:c.376-2A>G
NM_001126115.1:c.-23A>G
NM_001126116.1:c.-23A>G
NM_001126117.1:c.-23A>G

Links:

dbSNP: rs786202799

NCBI 1000 Genomes Browser:

rs786202799

Molecular consequence:

NM_001126115.2:c.-23A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001126116.2:c.-23A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001126117.2:c.-23A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276697.3:c.-104A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276698.3:c.-104A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276699.3:c.-104A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000546.6:c.376-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001126112.3:c.376-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001126113.3:c.376-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001126114.3:c.376-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001126118.2:c.259-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001276695.3:c.259-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001276696.3:c.259-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001276760.3:c.259-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001276761.3:c.259-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407262.1:c.376-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407263.1:c.259-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407264.1:c.376-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407265.1:c.259-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407266.1:c.376-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407267.1:c.259-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407268.1:c.376-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407269.1:c.259-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407270.1:c.376-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407271.1:c.259-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

Functional consequence:

sequence_variant_affecting_splicing [Sequence Ontology: SO:1000071] - Comment(s)

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000568762	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Apr 18, 2022)	germline	clinical testing	Citation Link,
SCV000925731	MutSpliceDB: a database of splice sites variants effects on splicing, NIH	no classification provided	not provided	not applicable	in vitro	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000568762

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Apr 18, 2022)

germline

clinical testing

Citation Link,

SCV000925731

MutSpliceDB: a database of splice sites variants effects on splicing, NIH

no classification provided

not provided

not applicable

in vitro

Citation Link

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	not applicable	not applicable	not provided	not provided	not provided	not provided	not provided	in vitro

Details of each submission

From GeneDx, SCV000568762.6

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

Description

Canonical splice site variant expected to result in aberrant splicing and demonstrated to result in an in-frame loss of seven amino acids (Chappuis 1999, Athanasakis 2014); Functional assays performed on tumor cells harboring this variant found reduced or absent transactivation of typical TP53 targets (Chappuis 1999, Athanasakis 2014, Agnoletto 2015); Observed in a kindred reported to have features of Li-Fraumeni syndrome and also identified in individuals with breast, colorectal, or ovarian cancer (Kupryjanczyk 1993, Wu 2011, Siraj 2017, Li 2019); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 21305319, 27189670, 10567903, 11595686, 24729566, 26857262, 25544776, 28497333, 8506342, 28975465, 15510160, 33790576, 29751042, 30720243, 29752822, 29070607, 25587027, 10864200)

#	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 MutSpliceDB: a database of splice sites variants effects on splicing, NIH, SCV000925731.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	in vitro	not provided

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

Last Updated: Sep 29, 2024

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