NM_000038.6(APC):c.721G>A (p.Glu241Lys) AND Familial adenomatous polyposis 1

replaced

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 19, 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:: RCV000461525.4

Allele description

NM_000038.6(APC):c.721G>A (p.Glu241Lys)

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.721G>A (p.Glu241Lys)

HGVS:

NC_000005.10:g.112792521G>A
NG_008481.4:g.105001G>A
NM_000038.6:c.721G>A
NM_001127510.3:c.721G>A
NM_001127511.3:c.676-8758G>A
NM_001354895.2:c.721G>A
NM_001354896.2:c.721G>A
NM_001354897.2:c.751G>A
NM_001354898.2:c.646G>A
NM_001354899.2:c.646-8758G>A
NM_001354900.2:c.544G>A
NM_001354901.2:c.544G>A
NM_001354902.2:c.751G>A
NM_001354903.2:c.721G>A
NM_001354904.2:c.646G>A
NM_001354905.2:c.544G>A
NM_001354906.2:c.-315G>A
NP_000029.2:p.Glu241Lys
NP_001120982.1:p.Glu241Lys
NP_001341824.1:p.Glu241Lys
NP_001341825.1:p.Glu241Lys
NP_001341826.1:p.Glu251Lys
NP_001341827.1:p.Glu216Lys
NP_001341829.1:p.Glu182Lys
NP_001341830.1:p.Glu182Lys
NP_001341831.1:p.Glu251Lys
NP_001341832.1:p.Glu241Lys
NP_001341833.1:p.Glu216Lys
NP_001341834.1:p.Glu182Lys
LRG_130:g.105001G>A
NC_000005.9:g.112128218G>A
NM_000038.5:c.721G>A

Protein change:

E182K

Links:

dbSNP: rs777603154

NCBI 1000 Genomes Browser:

rs777603154

Molecular consequence:

NM_001354906.2:c.-315G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001127511.3:c.676-8758G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001354899.2:c.646-8758G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000038.6:c.721G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001127510.3:c.721G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354895.2:c.721G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354896.2:c.721G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354897.2:c.751G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354898.2:c.646G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354900.2:c.544G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354901.2:c.544G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354902.2:c.751G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354903.2:c.721G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354904.2:c.646G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354905.2:c.544G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Familial adenomatous polyposis 1 (FAP1)
Synonyms:: Familial Adenomatous Polyposis; POLYPOSIS, ADENOMATOUS INTESTINAL; FAMILIAL ADENOMATOUS POLYPOSIS 1, ATTENUATED; See all synonyms [MedGen]
Identifiers:: MedGen: C2713442; OMIM: 175100

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000552564	Invitae	criteria provided, single submitter (Nykamp K et al. (Genet Med 2017))	Uncertain significance (Jun 19, 2018)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 29371908, 16616356, 15122587, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000552564

Invitae

criteria provided, single submitter

(Nykamp K et al. (Genet Med 2017))

Uncertain significance
(Jun 19, 2018)

germline

clinical testing

PubMed (4)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Genetic variants of prospectively demonstrated phenocopies in BRCA1/2 kindreds.

Dominguez-Valentin M, Evans DGR, Nakken S, Tubeuf H, Vodak D, Ekstrøm PO, Nissen AM, Morak M, Holinski-Feder E, Martins A, Møller P, Hovig E.

Hered Cancer Clin Pract. 2018;16:4. doi: 10.1186/s13053-018-0086-0.

PubMed [citation]

PMID:: 29371908
PMCID:: PMC5769521

Novel findings in Swedish patients with MYH-associated polyposis: mutation detection and clinical characterization.

Kanter-Smoler G, Björk J, Fritzell K, Engwall Y, Hallberg B, Karlsson G, Grönberg H, Karlsson P, Wallgren A, Wahlström J, Hultcrantz R, Nordling M.

Clin Gastroenterol Hepatol. 2006 Apr;4(4):499-506.

PubMed [citation]

PMID:: 16616356

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV000552564.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change replaces glutamic acid with lysine at codon 241 of the APC protein (p.Glu241Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs777603154, ExAC 0.02%). This variant has been observed in individuals affected with colorectal cancer, breast cancer, and MUTYH-associated colorectal adenomatous polyposis (PMID: 16616356, 15122587, 29371908). ClinVar contains an entry for this variant (Variation ID: 243106). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Nov 7, 2019

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