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NM_000038.6(APC):c.4612_4613del (p.Glu1538fs) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Mar 30, 2021
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:
RCV003227591.8

Allele description [Variation Report for NM_000038.6(APC):c.4612_4613del (p.Glu1538fs)]

NM_000038.6(APC):c.4612_4613del (p.Glu1538fs)

Gene:
APC:APC regulator of WNT signaling pathway [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
5q22.2
Genomic location:
Preferred name:
NM_000038.6(APC):c.4612_4613del (p.Glu1538fs)
HGVS:
  • NC_000005.10:g.112840206_112840207del
  • NG_008481.4:g.152685_152686del
  • NG_008481.4:g.152686_152687del
  • NM_000038.6:c.4612_4613delMANE SELECT
  • NM_001127510.3:c.4612_4613del
  • NM_001127511.3:c.4558_4559del
  • NM_001354895.2:c.4612_4613del
  • NM_001354896.2:c.4666_4667del
  • NM_001354897.2:c.4642_4643del
  • NM_001354898.2:c.4537_4538del
  • NM_001354899.2:c.4528_4529del
  • NM_001354900.2:c.4489_4490del
  • NM_001354901.2:c.4435_4436del
  • NM_001354902.2:c.4339_4340del
  • NM_001354903.2:c.4309_4310del
  • NM_001354904.2:c.4234_4235del
  • NM_001354905.2:c.4132_4133del
  • NM_001354906.2:c.3763_3764del
  • NP_000029.2:p.Glu1538fs
  • NP_001120982.1:p.Glu1538fs
  • NP_001120983.2:p.Glu1520fs
  • NP_001341824.1:p.Glu1538fs
  • NP_001341825.1:p.Glu1556fs
  • NP_001341826.1:p.Glu1548fs
  • NP_001341827.1:p.Glu1513fs
  • NP_001341828.1:p.Glu1510fs
  • NP_001341829.1:p.Glu1497fs
  • NP_001341830.1:p.Glu1479fs
  • NP_001341831.1:p.Glu1447fs
  • NP_001341832.1:p.Glu1437fs
  • NP_001341833.1:p.Glu1412fs
  • NP_001341834.1:p.Glu1378fs
  • NP_001341835.1:p.Glu1255fs
  • LRG_130:g.152686_152687del
  • NC_000005.10:g.112840206_112840207delGA
  • NC_000005.9:g.112175902_112175903del
  • NC_000005.9:g.112175903_112175904del
  • NG_008481.4:g.152685_152686del
  • NM_000038.5:c.4612_4613delGA
Protein change:
E1255fs
Links:
OMIM: 611731.0030; dbSNP: rs387906236
NCBI 1000 Genomes Browser:
rs387906236
Molecular consequence:
  • NM_000038.6:c.4612_4613del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001127510.3:c.4612_4613del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001127511.3:c.4558_4559del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354895.2:c.4612_4613del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354896.2:c.4666_4667del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354897.2:c.4642_4643del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354898.2:c.4537_4538del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354899.2:c.4528_4529del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354900.2:c.4489_4490del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354901.2:c.4435_4436del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354902.2:c.4339_4340del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354903.2:c.4309_4310del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354904.2:c.4234_4235del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354905.2:c.4132_4133del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354906.2:c.3763_3764del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Desmoid disease, hereditary (DESMD)
Synonyms:
Fibromatosis, familial infiltrative
Identifiers:
MedGen: C1851124; Orphanet: 873; OMIM: 135290
Name:
Familial adenomatous polyposis 1 (FAP1)
Synonyms:
POLYPOSIS, ADENOMATOUS INTESTINAL; FAMILIAL ADENOMATOUS POLYPOSIS 1, ATTENUATED; APC-Associated Polyposis Conditions
Identifiers:
MONDO: MONDO:0021056; MedGen: C2713442; OMIM: 175100
Name:
Hepatocellular carcinoma (HCC)
Synonyms:
Primary carcinoma of liver; Hepatoma; LIVER CELL CARCINOMA; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0007256; MedGen: C2239176; OMIM: 114550; Human Phenotype Ontology: HP:0001402
Name:
Gastric cancer
Synonyms:
Stomach cancer; Malignant tumor of stomach
Identifiers:
MONDO: MONDO:0001056; MeSH: D013274; MedGen: C0024623; OMIM: 613659; Human Phenotype Ontology: HP:0012126
Name:
Colorectal cancer
Synonyms:
Colorectal cancer, somatic; Malignant Colorectal Neoplasm
Identifiers:
MONDO: MONDO:0005575; MedGen: C0346629; OMIM: 114500
Name:
Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS)
Synonyms:
POLYPOSIS, GASTRIC; Polyposis, gastric, Dos Santos and de Magalhaes 1980
Identifiers:
MONDO: MONDO:0017790; MedGen: C4749917; OMIM: 619182

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003924235Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Mar 30, 2021) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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 Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago, SCV003924235.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

APC NM_000038.5 exon 15 p.Glu1538Ilefsx5 (c.4612_4613del): This variant has been reported in the literature in at least 8 individuals with Familial Adenomatous Polyposis (FAP) (Gayther 1994 PMID:8162051, Friedl 2005 PMID:20223039, Jang 2010 PMID:20513532, Lagarde 2010 PMID:20685668, Jarry 2011 PMID:21779980, Rohlin 2011 PMID:21643010, Schwarzova 2013 PMID:22987206). This variant is not present in large control databases. This variant is present in ClinVar (Variation ID:823). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. This variant is a deletion of two nucleotides and creates a premature stop codon 5 amino acids downstream from this location which results in an absent or abnormal protein. Loss of function variants are a known mechanism of disease for this gene (Zhang 2017 PMID:28423402). Of note, this variant occurs within the last exon of this gene; due to its position, it is possible that this protein may escape nonsense mediated decay. However this variant is predicted to affect approximately 45% of the protein and other variants downstream have been reported as Pathogenic. Furthermore, evidence in the literature suggests that variants cluster in this region (Gayther 1994 PMID:8162051). In summary, this variant is classified as pathogenic based on the data above.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 13, 2024