NM_000546.6(TP53):c.375+2T>A AND Hereditary cancer-predisposing syndrome

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Jun 18, 2022
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:: RCV001021046.5

Allele description [Variation Report for NM_000546.6(TP53):c.375+2T>A]

NM_000546.6(TP53):c.375+2T>A

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.375+2T>A

HGVS:

NC_000017.11:g.7675992A>T
NG_017013.2:g.16559T>A
NM_000546.6:c.375+2T>AMANE SELECT
NM_001126112.3:c.375+2T>A
NM_001126113.3:c.375+2T>A
NM_001126114.3:c.375+2T>A
NM_001126118.2:c.258+2T>A
NM_001276695.3:c.258+2T>A
NM_001276696.3:c.258+2T>A
NM_001276760.3:c.258+2T>A
NM_001276761.3:c.258+2T>A
NM_001407262.1:c.375+2T>A
NM_001407263.1:c.258+2T>A
NM_001407264.1:c.375+2T>A
NM_001407265.1:c.258+2T>A
NM_001407266.1:c.375+2T>A
NM_001407267.1:c.258+2T>A
NM_001407268.1:c.375+2T>A
NM_001407269.1:c.258+2T>A
NM_001407270.1:c.375+2T>A
NM_001407271.1:c.258+2T>A
LRG_321t1:c.375+2T>A
LRG_321:g.16559T>A
NC_000017.10:g.7579310A>T
NM_000546.4:c.375+2T>A
NM_000546.5:c.375+2T>A

Links:

dbSNP: rs1555526469

NCBI 1000 Genomes Browser:

rs1555526469

Molecular consequence:

NM_000546.6:c.375+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001126112.3:c.375+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001126113.3:c.375+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001126114.3:c.375+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001126118.2:c.258+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001276695.3:c.258+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001276696.3:c.258+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001276760.3:c.258+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001276761.3:c.258+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407262.1:c.375+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407263.1:c.258+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407264.1:c.375+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407265.1:c.258+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407266.1:c.375+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407267.1:c.258+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407268.1:c.375+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407269.1:c.258+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407270.1:c.375+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407271.1:c.258+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]

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

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
SCV001182609	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Jun 17, 2019)	germline	clinical testing	Citation Link,
SCV002582400	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jun 18, 2022)	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

SCV001182609

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Jun 17, 2019)

germline

clinical testing

Citation Link,

SCV002582400

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jun 18, 2022)

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	no	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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Ambry Genetics, SCV001182609.4

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

Description

The c.375+2T>A intronic variant results from a T to A substitution two nucleotides after coding exon 3 in the TP53 gene. This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice donor site; however, direct evidence is unavailable. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely 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

From Genome-Nilou Lab, SCV002582400.1

#	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	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 10, 2024

ClinVar

Relating variation to medicine