NM_000038.6(APC):c.5822_5825CAGA[1] (p.Asp1942fs) AND Familial adenomatous polyposis 1

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 12, 2016
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:: RCV000206426.2

Allele description

NM_000038.6(APC):c.5822_5825CAGA[1] (p.Asp1942fs)

Gene:

APC:APC regulator of WNT signaling pathway [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

5q22.2

Genomic location:

Preferred name:

NM_000038.6(APC):c.5822_5825CAGA[1] (p.Asp1942fs)

HGVS:

NC_000005.10:g.112841416_112841419CAGA[1]
NG_008481.4:g.153896_153899CAGA[1]
NM_000038.6:c.5822_5825CAGA[1]MANE SELECT
NM_001127510.3:c.5822_5825CAGA[1]
NM_001127511.3:c.5768_5771CAGA[1]
NM_001354895.2:c.5822_5825CAGA[1]
NM_001354896.2:c.5876_5879CAGA[1]
NM_001354897.2:c.5852_5855CAGA[1]
NM_001354898.2:c.5747_5750CAGA[1]
NM_001354899.2:c.5738_5741CAGA[1]
NM_001354900.2:c.5699_5702CAGA[1]
NM_001354901.2:c.5645_5648CAGA[1]
NM_001354902.2:c.5549_5552CAGA[1]
NM_001354903.2:c.5519_5522CAGA[1]
NM_001354904.2:c.5444_5447CAGA[1]
NM_001354905.2:c.5342_5345CAGA[1]
NM_001354906.2:c.4973_4976CAGA[1]
NP_000029.2:p.Asp1942fs
NP_001120982.1:p.Asp1942fs
NP_001120983.2:p.Asp1924fs
NP_001341824.1:p.Asp1942fs
NP_001341825.1:p.Asp1960fs
NP_001341826.1:p.Asp1952fs
NP_001341827.1:p.Asp1917fs
NP_001341828.1:p.Asp1914fs
NP_001341829.1:p.Asp1901fs
NP_001341830.1:p.Asp1883fs
NP_001341831.1:p.Asp1851fs
NP_001341832.1:p.Asp1841fs
NP_001341833.1:p.Asp1816fs
NP_001341834.1:p.Asp1782fs
NP_001341835.1:p.Asp1659fs
LRG_130:g.153896_153899CAGA[1]
NC_000005.9:g.112177113_112177116CAGA[1]
NM_000038.5:c.5826_5829delCAGA
p.Asp1942Glufs*27

Note:

NCBI staff could not confirm the published nucleotide change on current reference sequence after review of PubMed 8968744.

Links:

OMIM: 611731.0026; dbSNP: rs864622228

NCBI 1000 Genomes Browser:

rs864622228

Molecular consequence:

NM_000038.6:c.5822_5825CAGA[1] - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001127510.3:c.5822_5825CAGA[1] - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001127511.3:c.5768_5771CAGA[1] - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354895.2:c.5822_5825CAGA[1] - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354896.2:c.5876_5879CAGA[1] - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354897.2:c.5852_5855CAGA[1] - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354898.2:c.5747_5750CAGA[1] - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354899.2:c.5738_5741CAGA[1] - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354900.2:c.5699_5702CAGA[1] - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354901.2:c.5645_5648CAGA[1] - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354902.2:c.5549_5552CAGA[1] - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354903.2:c.5519_5522CAGA[1] - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354904.2:c.5444_5447CAGA[1] - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354905.2:c.5342_5345CAGA[1] - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354906.2:c.4973_4976CAGA[1] - frameshift variant - [Sequence Ontology: SO:0001589]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000259788	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 12, 2016)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000259788

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 12, 2016)

germline

clinical testing

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

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

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, SCV000259788.3

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

Description

This sequence change deletes 4 nucleotides from exon 16 of the APC mRNA (c.5826_5829delCAGA), causing a frameshift at codon 1942. This creates a premature translational stop signal in the last exon of the APC mRNA (p.Asp1942Glufs*27). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 902 amino acids of the APC protein. Loss-of-function variants in APC are known to be pathogenic. This particular variant has been reported in the literature in individuals with a personal or family history of desmoid tumors (PMID: 8968744), and a personal or family history of familial adenomatous polyposis (PMID: 15108286, 11001924). This variant has been also been reported in an infant affected with Gardner fibroma with suspected desmoid tumor (PMID: 25074465). In this family, the variant was also observed in the proband's father, who had polyposis. The proband's paternal grandfather, affected with polyposis and colon cancer, is an obligate carrier. Sequencing of the proband's tumor revealed a somatic pathogenic APC mutation (p.Lys560*). This variant is also known as 5824delGACA and 5844_5847del4 in the literature. For these reasons, this variant has been classified as Pathogenic.

#	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: Jul 3, 2020

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