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NM_000038.6(APC):c.532-8G>A AND Carcinoma of colon

Germline classification:
Likely pathogenic (1 submission)
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV000503571.12

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]
Observations:
1

Condition(s)

Name:
Carcinoma of colon (CRC)
Synonyms:
Colonic carcinoma; Colon carcinoma
Identifiers:
MONDO: MONDO:0002032; MedGen: C0699790

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000591038Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR)

See additional submitters

no assertion criteria provided
Likely pathogenicunknownclinical testing

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownyes1not providednot providednot providednot providedclinical testing

Details of each submission

From Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV000591038.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided

Description

The APC c.532-8G>A variant was identified by Kaufmann (2009) in a German individual with FAP. The variant was also identified InSiGHT Colon Cancer Gene Variant Database 3x as a splice mutation, and UMD (2x as a causal variant). The variant was not found in dbSNP, NHLBI Exome Sequencing Project (Exome Variant Server), Exome Aggregation Consortium (ExAC) database, Clinvitae database, COSMIC, “Mismatch Repair Genes Variant Database”, “MMR Gene Unclassified Variants Database”, “Zhejiang Colon Cancer Database”, the ClinVar database, or GeneInsight COGR database. The variant occurs outside of the splicing consensus sequence and 5 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing. However, this information is not predictive enough to assume pathogenicity. A functional study by Kaufmann (2009) found that the variant introduced a new splice acceptor site, creating a premature stop codon because of aberrant splicing producing an out-of-frame transcript. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more pathogenic role for this variant. This variant is classified as predicted pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownyesnot providednot providednot provided1not providednot providednot provided

Last Updated: Sep 1, 2024