NM_000038.6(APC):c.4732T>G (p.Cys1578Gly) AND Familial adenomatous polyposis 1

Clinical significance:Likely pathogenic (Last evaluated: Sep 21, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000206222.8

Allele description [Variation Report for NM_000038.6(APC):c.4732T>G (p.Cys1578Gly)]

NM_000038.6(APC):c.4732T>G (p.Cys1578Gly)

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.4732T>G (p.Cys1578Gly)
HGVS:
  • NC_000005.10:g.112840326T>G
  • NG_008481.4:g.152806T>G
  • NM_000038.6:c.4732T>GMANE SELECT
  • NM_001127510.3:c.4732T>G
  • NM_001127511.3:c.4678T>G
  • NM_001354895.2:c.4732T>G
  • NM_001354896.2:c.4786T>G
  • NM_001354897.2:c.4762T>G
  • NM_001354898.2:c.4657T>G
  • NM_001354899.2:c.4648T>G
  • NM_001354900.2:c.4609T>G
  • NM_001354901.2:c.4555T>G
  • NM_001354902.2:c.4459T>G
  • NM_001354903.2:c.4429T>G
  • NM_001354904.2:c.4354T>G
  • NM_001354905.2:c.4252T>G
  • NM_001354906.2:c.3883T>G
  • NP_000029.2:p.Cys1578Gly
  • NP_001120982.1:p.Cys1578Gly
  • NP_001120983.2:p.Cys1560Gly
  • NP_001341824.1:p.Cys1578Gly
  • NP_001341825.1:p.Cys1596Gly
  • NP_001341826.1:p.Cys1588Gly
  • NP_001341827.1:p.Cys1553Gly
  • NP_001341828.1:p.Cys1550Gly
  • NP_001341829.1:p.Cys1537Gly
  • NP_001341830.1:p.Cys1519Gly
  • NP_001341831.1:p.Cys1487Gly
  • NP_001341832.1:p.Cys1477Gly
  • NP_001341833.1:p.Cys1452Gly
  • NP_001341834.1:p.Cys1418Gly
  • NP_001341835.1:p.Cys1295Gly
  • LRG_130:g.152806T>G
  • NC_000005.9:g.112176023T>G
  • NM_000038.5:c.4732T>G
  • NM_001127510.2:c.4732T>G
  • p.C1578G
Protein change:
C1295G
Links:
dbSNP: rs138367627
NCBI 1000 Genomes Browser:
rs138367627
Molecular consequence:
  • NM_000038.6:c.4732T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127510.3:c.4732T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127511.3:c.4678T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354895.2:c.4732T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354896.2:c.4786T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354897.2:c.4762T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354898.2:c.4657T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354899.2:c.4648T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354900.2:c.4609T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354901.2:c.4555T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354902.2:c.4459T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354903.2:c.4429T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354904.2:c.4354T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354905.2:c.4252T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354906.2:c.3883T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000260260Invitaecriteria provided, single submitter
Likely pathogenic
(Sep 21, 2020)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Multiple rare nonsynonymous variants in the adenomatous polyposis coli gene predispose to colorectal adenomas.

Azzopardi D, Dallosso AR, Eliason K, Hendrickson BC, Jones N, Rawstorne E, Colley J, Moskvina V, Frye C, Sampson JR, Wenstrup R, Scholl T, Cheadle JP.

Cancer Res. 2008 Jan 15;68(2):358-63. doi: 10.1158/0008-5472.CAN-07-5733.

PubMed [citation]
PMID:
18199528

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000260260.9

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces cysteine with glycine at codon 1578 of the APC protein (p.Cys1578Gly). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals with clinical features of familial adenomatous polyposis (PMID: 18199528, Invitae). ClinVar contains an entry for this variant (Variation ID: 140839). This variant has been reported to have conflicting or insufficient data to determine the effect on APC protein (PMID: 18199528). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: Nov 27, 2021

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