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NM_001127511.3(APC):c.-191T>C AND Gastric adenocarcinoma and proximal polyposis of the stomach

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Feb 23, 2021
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:
RCV001290975.11

Allele description [Variation Report for NM_001127511.3(APC):c.-191T>C]

NM_001127511.3(APC):c.-191T>C

Genes:
APC:APC regulator of WNT signaling pathway [Gene - OMIM - HGNC]
LOC129994371:ATAC-STARR-seq lymphoblastoid active region 22910 [Gene]
Variant type:
single nucleotide variant
Cytogenetic location:
5q22.2
Genomic location:
Preferred name:
NM_001127511.3(APC):c.-191T>C
HGVS:
  • NC_000005.10:g.112707527T>C
  • NG_008481.4:g.20007T>C
  • NG_173817.1:g.150T>C
  • NM_001127511.3:c.-191T>C
  • NM_001354895.2:c.-374T>C
  • NM_001354897.2:c.-191T>C
  • NM_001354902.2:c.-191T>C
  • NM_001407446.1:c.-191T>C
  • NM_001407447.1:c.-374T>C
  • NM_001407448.1:c.-141T>C
  • NM_001407450.1:c.-141T>C
  • NM_001407452.1:c.-374T>C
  • NM_001407453.1:c.-165T>C
  • NM_001407456.1:c.-374T>C
  • NM_001407457.1:c.-141T>C
  • NM_001407458.1:c.-141T>C
  • NM_001407460.1:c.-374T>C
  • NM_001407469.1:c.-374T>C
  • NM_001407470.1:c.-1409T>C
  • NM_001407472.1:c.-1409T>C
  • LRG_130t3:c.-374T>C
  • LRG_130:g.20007T>C
  • NC_000005.9:g.112043224T>C
  • NM_000038.5:c.-30417T>C
  • NM_001127511.1:c.-374T>C
  • NM_001127511.2:c.-191T>C
  • NR_176365.1:n.30T>C
  • NR_176366.1:n.30T>C
Nucleotide change:
-191T-C
Links:
OMIM: 611731.0054; dbSNP: rs879253783
NCBI 1000 Genomes Browser:
rs879253783
Molecular consequence:
  • NM_001127511.3:c.-191T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354895.2:c.-374T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354897.2:c.-191T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354902.2:c.-191T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001407446.1:c.-191T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001407447.1:c.-374T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001407448.1:c.-141T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001407450.1:c.-141T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001407452.1:c.-374T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001407453.1:c.-165T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001407456.1:c.-374T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001407457.1:c.-141T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001407458.1:c.-141T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001407460.1:c.-374T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001407469.1:c.-374T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001407470.1:c.-1409T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001407472.1:c.-1409T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NR_176365.1:n.30T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_176366.1:n.30T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

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

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000292336OMIM
no assertion criteria provided
Pathogenic
(Feb 23, 2021)
germlineliterature only

PubMed (6)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS): a new autosomal dominant syndrome.

Worthley DL, Phillips KD, Wayte N, Schrader KA, Healey S, Kaurah P, Shulkes A, Grimpen F, Clouston A, Moore D, Cullen D, Ormonde D, Mounkley D, Wen X, Lindor N, Carneiro F, Huntsman DG, Chenevix-Trench G, Suthers GK.

Gut. 2012 May;61(5):774-9. doi: 10.1136/gutjnl-2011-300348. Epub 2011 Aug 3. Erratum in: Gut. 2012 Sep;61(9):1305.

PubMed [citation]
PMID:
21813476

Point Mutations in Exon 1B of APC Reveal Gastric Adenocarcinoma and Proximal Polyposis of the Stomach as a Familial Adenomatous Polyposis Variant.

Li J, Woods SL, Healey S, Beesley J, Chen X, Lee JS, Sivakumaran H, Wayte N, Nones K, Waterfall JJ, Pearson J, Patch AM, Senz J, Ferreira MA, Kaurah P, Mackenzie R, Heravi-Moussavi A, Hansford S, Lannagan TRM, Spurdle AB, Simpson PT, da Silva L, et al.

Am J Hum Genet. 2016 May 5;98(5):830-842. doi: 10.1016/j.ajhg.2016.03.001. Epub 2016 Apr 14.

PubMed [citation]
PMID:
27087319
PMCID:
PMC4863475
See all PubMed Citations (6)

Details of each submission

From OMIM, SCV000292336.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (6)

Description

In 4 families (2, 4, 5, and 6) with gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS; 619182), 1 of which was the US family originally described by Worthley et al. (2012) as family 2, Li et al. (2016) identified heterozygosity for a c.-191T-C transition (c.-191T-C, NM_001127511) in a YY1 binding motif of the APC promoter 1B that segregated with disease in all 4 families and was not found in 344 germline samples from an in-house WGS cancer project or in the 1000 Genomes Project database. By EMSA, Li et al. (2016) demonstrated that the c.-191T-C mutation disrupts binding to the promoter 1B region in both AGS and RKO cells. In luciferase reporter assays, constructs with c.-191T-C showed significantly decreased activity compared to wildtype.

In a father and 3 daughters from a 3-generation Czech family with GAPPS, Repak et al. (2016) identified heterozygosity for the c.-191T-C variant in the APC promoter 1B. DNA analysis was not reported for the paternal grandmother who also had proximal gastric polyposis and died of gastric cancer at age 49 years.

In a 38-year-old Austrian woman with GAPPS, Beer et al. (2017) identified heterozygosity for the c.-191T-C variant in the APC promoter 1B. DNA was unavailable from her father, who died of gastric cancer at age 57 years.

In 24 individuals from 8 Czech families with GAPPS, Foretova et al. (2019) identified heterozygosity for the c.-191T-C variant in the APC promoter 1B. Of the 24 mutation carriers, 20 had massive gastric polyposis; in addition, 1 female carrier had incipient polyposis at age 58 years, 2 female carriers did not have polyposis of the stomach at ages 31 and 65, and a 92-year-old asymptomatic male carrier did not undergo gastroscopy due to his advanced age.

In affected members of 2 multiplex Japanese families with GAPPS, Kanemitsu et al. (2021) identified heterozygosity for the c.-191T-C variant in the APC promoter 1B.

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

Last Updated: Nov 10, 2024