NM_000038.6(APC):c.532-8G>A AND Familial multiple polyposis syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Sep 6, 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:: RCV002298605.8

Allele description [Variation Report for NM_000038.6(APC):c.532-8G>A]

NM_000038.6(APC):c.532-8G>A

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.532-8G>A

HGVS:

NC_000005.10:g.112780782G>A
NG_008481.4:g.93262G>A
NM_000038.6:c.532-8G>AMANE SELECT
NM_001127510.3:c.532-8G>A
NM_001127511.3:c.562-8G>A
NM_001354895.2:c.532-8G>A
NM_001354896.2:c.532-8G>A
NM_001354897.2:c.562-8G>A
NM_001354898.2:c.457-8G>A
NM_001354899.2:c.532-8G>A
NM_001354900.2:c.355-8G>A
NM_001354901.2:c.355-8G>A
NM_001354902.2:c.562-8G>A
NM_001354903.2:c.532-8G>A
NM_001354904.2:c.457-8G>A
NM_001354905.2:c.355-8G>A
NM_001354906.2:c.-504-8G>A
LRG_130:g.93262G>A
NC_000005.9:g.112116479G>A
NM_000038.5:c.532-8G>A

Links:

dbSNP: rs1060503323

NCBI 1000 Genomes Browser:

rs1060503323

Molecular consequence:

NM_000038.6:c.532-8G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001127510.3:c.532-8G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001127511.3:c.562-8G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001354895.2:c.532-8G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001354896.2:c.532-8G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001354897.2:c.562-8G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001354898.2:c.457-8G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001354899.2:c.532-8G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001354900.2:c.355-8G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001354901.2:c.355-8G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001354902.2:c.562-8G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001354903.2:c.532-8G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001354904.2:c.457-8G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001354905.2:c.355-8G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001354906.2:c.-504-8G>A - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Familial multiple polyposis syndrome (FAP)
Synonyms:: Familial adenomatous polyposis of the colon; Familial polyposis of the colon; Familial intestinal polyposis; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0021055; MedGen: C0032580; OMIM: PS175100

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002598594	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (Sep 6, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 24599579, 19196998 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002598594

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely pathogenic
(Sep 6, 2022)

germline

clinical testing

PubMed (2)
[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

The UMD-APC database, a model of nation-wide knowledge base: update with data from 3,581 variations.

Grandval P, Blayau M, Buisine MP, Coulet F, Maugard C, Pinson S, Remenieras A, Tinat J, Uhrhammer N, Béroud C, Olschwang S.

Hum Mutat. 2014 May;35(5):532-6. doi: 10.1002/humu.22539. Epub 2014 Apr 7.

PubMed [citation]

PMID:: 24599579

Analysis of rare APC variants at the mRNA level: six pathogenic mutations and literature review.

Kaufmann A, Vogt S, Uhlhaas S, Stienen D, Kurth I, Hameister H, Mangold E, Kötting J, Kaminsky E, Propping P, Friedl W, Aretz S.

J Mol Diagn. 2009 Mar;11(2):131-9. doi: 10.2353/jmoldx.2009.080129. Epub 2009 Feb 5. Review.

PubMed [citation]

PMID:: 19196998
PMCID:: PMC2665862

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002598594.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

Variant summary: APC c.532-8G>A alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Multiple computational tools predict a significant impact on normal splicing: Four predict the variant creates a cryptic 3' acceptor site, replacing the wildtype site and creating a premature stop codon. At least one publication reports experimental evidence that this variant affects mRNA splicing (Kaufmann_2009, Grandval_2014). The variant was absent in 247292 control chromosomes. c.532-8G>A has been reported in the literature in individuals affected with Familial Adenomatous Polyposis (Kaufmann_2009). Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was 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

Last Updated: Nov 3, 2024

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