NM_000038.6(APC):c.637C>T (p.Arg213Ter) AND Familial multiple polyposis syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 17, 2018
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:: RCV000825611.14

Allele description [Variation Report for NM_000038.6(APC):c.637C>T (p.Arg213Ter)]

NM_000038.6(APC):c.637C>T (p.Arg213Ter)

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.637C>T (p.Arg213Ter)

Other names:

p.R213*:CGA>TGA; NM_000038.4:c.637C>T; p.Arg213X

HGVS:

NC_000005.10:g.112780895C>T
NG_008481.4:g.93375C>T
NM_000038.6:c.637C>TMANE SELECT
NM_001127510.3:c.637C>T
NM_001127511.3:c.667C>T
NM_001354895.2:c.637C>T
NM_001354896.2:c.637C>T
NM_001354897.2:c.667C>T
NM_001354898.2:c.562C>T
NM_001354899.2:c.637C>T
NM_001354900.2:c.460C>T
NM_001354901.2:c.460C>T
NM_001354902.2:c.667C>T
NM_001354903.2:c.637C>T
NM_001354904.2:c.562C>T
NM_001354905.2:c.460C>T
NM_001354906.2:c.-399C>T
NP_000029.2:p.Arg213Ter
NP_001120982.1:p.Arg213Ter
NP_001120983.2:p.Arg223Ter
NP_001341824.1:p.Arg213Ter
NP_001341825.1:p.Arg213Ter
NP_001341826.1:p.Arg223Ter
NP_001341827.1:p.Arg188Ter
NP_001341828.1:p.Arg213Ter
NP_001341829.1:p.Arg154Ter
NP_001341830.1:p.Arg154Ter
NP_001341831.1:p.Arg223Ter
NP_001341832.1:p.Arg213Ter
NP_001341833.1:p.Arg188Ter
NP_001341834.1:p.Arg154Ter
LRG_130:g.93375C>T
NC_000005.9:g.112116592C>T
NM_000038.5:c.637C>T
p.Arg213*
p.R213*

Protein change:

R154*

Links:

dbSNP: rs587781392

NCBI 1000 Genomes Browser:

rs587781392

Molecular consequence:

NM_001354906.2:c.-399C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000038.6:c.637C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001127510.3:c.637C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001127511.3:c.667C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001354895.2:c.637C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001354896.2:c.637C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001354897.2:c.667C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001354898.2:c.562C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001354899.2:c.637C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001354900.2:c.460C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001354901.2:c.460C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001354902.2:c.667C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001354903.2:c.637C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001354904.2:c.562C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001354905.2:c.460C>T - nonsense - [Sequence Ontology: SO:0001587]

Observations:

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
SCV000966956	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Pathogenic (Apr 17, 2018)	germline	clinical testing	PubMed (11) [See all records that cite these PMIDs] 17411426, 10094547, 15857185, 25525159, 1316610, 26681312, 20685668, 20223039, 15024739, 26138249, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000966956

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Pathogenic
(Apr 17, 2018)

germline

clinical testing

PubMed (11)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	1	1	not provided	not provided	not provided	clinical testing

Citations

PubMed

Novel APC mutations in Czech and Slovak FAP families: clinical and genetic aspects.

Stekrova J, Sulova M, Kebrdlova V, Zidkova K, Kotlas J, Ilencikova D, Vesela K, Kohoutova M.

BMC Med Genet. 2007 Apr 5;8:16.

PubMed [citation]

PMID:: 17411426
PMCID:: PMC1853078

Screening for mutations of the APC gene in 66 Italian familial adenomatous polyposis patients: evidence for phenotypic differences in cases with and without identified mutation.

Giarola M, Stagi L, Presciuttini S, Mondini P, Radice MT, Sala P, Pierotti MA, Bertario L, Radice P.

Hum Mutat. 1999;13(2):116-23.

PubMed [citation]

PMID:: 10094547

See all PubMed Citations (11)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000966956.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (11)

Description

The p.Arg213X variant in APC has been reported in >15 individuals with APC-assoc iated cancers (Miyoshi 1992, Giarola 1999, Stekrova 2006, Friedl 2005, Garcia-L azano 2005, Lagarde 2010, Susswein 2016) and was absent from large population st udies. This variant has been reported as a somatic variant in >90 tumor samples from various cancer types, including colorectal cancer (The Catalogue of Somatic Mutations in Cancer, https://cancer.sanger.ac.uk/cosmic). This variant has also been reported in ClinVar (Variant ID: 140952). This nonsense variant leads to a premature termination codon at position 213, which is predicted to lead to a tr uncated or absent protein. Heterozygous loss of function of the APC gene is an e stablished disease mechanism in individuals with familial adenomatous polyposis (FAP). In summary, this variant meets criteria to be classified as pathogenic fo r FAP in an autosomal dominant manner based upon predicted impact to the protein , presence in affected individuals, and absence in the general population. ACMG/ AMP Criteria applied: PVS1; PS4; PM2.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		1	not provided	1	not provided

Last Updated: Oct 20, 2024

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