NM_000038.6(APC):c.646-2A>G AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 30, 2017
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:: RCV002367986.9

Allele description [Variation Report for NM_000038.6(APC):c.646-2A>G]

NM_000038.6(APC):c.646-2A>G

Gene:

APC:APC regulator of WNT signaling pathway [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q22.2

Genomic location:

Preferred name:

NM_000038.6(APC):c.646-2A>G

HGVS:

NC_000005.10:g.112792444A>G
NG_008481.4:g.104924A>G
NM_000038.6:c.646-2A>GMANE SELECT
NM_001127510.3:c.646-2A>G
NM_001127511.3:c.676-8835A>G
NM_001354895.2:c.646-2A>G
NM_001354896.2:c.646-2A>G
NM_001354897.2:c.676-2A>G
NM_001354898.2:c.571-2A>G
NM_001354899.2:c.646-8835A>G
NM_001354900.2:c.469-2A>G
NM_001354901.2:c.469-2A>G
NM_001354902.2:c.676-2A>G
NM_001354903.2:c.646-2A>G
NM_001354904.2:c.571-2A>G
NM_001354905.2:c.469-2A>G
NM_001354906.2:c.-390-2A>G
NM_001407446.1:c.676-2A>G
NM_001407447.1:c.646-2A>G
NM_001407448.1:c.646-2A>G
NM_001407449.1:c.646-2A>G
NM_001407450.1:c.646-2A>G
NM_001407451.1:c.571-2A>G
NM_001407452.1:c.646-8835A>G
NM_001407453.1:c.469-2A>G
NM_001407454.1:c.646-2A>G
NM_001407455.1:c.646-2A>G
NM_001407456.1:c.646-2A>G
NM_001407457.1:c.646-2A>G
NM_001407458.1:c.646-2A>G
NM_001407459.1:c.646-2A>G
NM_001407460.1:c.646-2A>G
NM_001407467.1:c.646-8835A>G
NM_001407469.1:c.646-8835A>G
NM_001407470.1:c.-390-2A>G
NM_001407471.1:c.-390-2A>G
NM_001407472.1:c.-390-2A>G
LRG_130:g.104924A>G
NC_000005.9:g.112128141A>G
NM_000038.5:c.646-2A>G

Links:

dbSNP: rs777848503

NCBI 1000 Genomes Browser:

rs777848503

Molecular consequence:

NM_001127511.3:c.676-8835A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001354899.2:c.646-8835A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001407452.1:c.646-8835A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001407467.1:c.646-8835A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001407469.1:c.646-8835A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000038.6:c.646-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001127510.3:c.646-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354895.2:c.646-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354896.2:c.646-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354897.2:c.676-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354898.2:c.571-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354900.2:c.469-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354901.2:c.469-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354902.2:c.676-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354903.2:c.646-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354904.2:c.571-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354905.2:c.469-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354906.2:c.-390-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407446.1:c.676-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407447.1:c.646-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407448.1:c.646-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407449.1:c.646-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407450.1:c.646-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407451.1:c.571-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407453.1:c.469-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407454.1:c.646-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407455.1:c.646-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407456.1:c.646-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407457.1:c.646-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407458.1:c.646-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407459.1:c.646-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407460.1:c.646-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407470.1:c.-390-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407471.1:c.-390-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407472.1:c.-390-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

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
SCV002659674	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Jan 30, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002659674

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Jan 30, 2017)

germline

clinical testing

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

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

Germline APC mutation spectrum derived from 863 genomic variations identified through a 15-year medical genetics service to French patients with FAP.

Lagarde A, Rouleau E, Ferrari A, Noguchi T, Qiu J, Briaux A, Bourdon V, Rémy V, Gaildrat P, Adélaïde J, Birnbaum D, Lidereau R, Sobol H, Olschwang S.

J Med Genet. 2010 Oct;47(10):721-2. doi: 10.1136/jmg.2010.078964. Epub 2010 Aug 3.

PubMed [citation]

PMID:: 20685668

Details of each submission

From Ambry Genetics, SCV002659674.2

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

Description

The c.646-2A>G intronic pathogenic mutation results from an A to G substitution two nucleotides upstream from coding exon 6 in the APC gene. This alteration was previously identified in a French cohort of patients with FAP (Lagarde A et al. J. Med. Genet. 2010 Oct;47:721-2). In addition to the clinical data presented in the literature, 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 a disease-causing mutation.

#	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: Oct 13, 2024

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