NM_000038.6(APC):c.5979del (p.Asp1994fs) AND Familial adenomatous polyposis 1

delete

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 21, 2022
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:: RCV002239307.15

Allele description

NM_000038.6(APC):c.5979del (p.Asp1994fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

5q22.2

Genomic location:

Preferred name:

NM_000038.6(APC):c.5979del (p.Asp1994fs)

HGVS:

NC_000005.10:g.112841573del
NG_008481.4:g.154053del
NM_000038.6:c.5979delMANE SELECT
NM_001127510.3:c.5979del
NM_001127511.3:c.5925del
NM_001354895.2:c.5979del
NM_001354896.2:c.6033del
NM_001354897.2:c.6009del
NM_001354898.2:c.5904del
NM_001354899.2:c.5895del
NM_001354900.2:c.5856del
NM_001354901.2:c.5802del
NM_001354902.2:c.5706del
NM_001354903.2:c.5676del
NM_001354904.2:c.5601del
NM_001354905.2:c.5499del
NM_001354906.2:c.5130del
NP_000029.2:p.Asp1994fs
NP_001120982.1:p.Asp1994fs
NP_001120983.2:p.Asp1976fs
NP_001341824.1:p.Asp1994fs
NP_001341825.1:p.Asp2012fs
NP_001341826.1:p.Asp2004fs
NP_001341827.1:p.Asp1969fs
NP_001341828.1:p.Asp1966fs
NP_001341829.1:p.Asp1953fs
NP_001341830.1:p.Asp1935fs
NP_001341831.1:p.Asp1903fs
NP_001341832.1:p.Asp1893fs
NP_001341833.1:p.Asp1868fs
NP_001341834.1:p.Asp1834fs
NP_001341835.1:p.Asp1711fs
LRG_130:g.154053del
NC_000005.9:g.112177270del
NM_000038.5:c.5979del

Protein change:

D1711fs

Links:

dbSNP: rs1766105693

NCBI 1000 Genomes Browser:

rs1766105693

Molecular consequence:

NM_000038.6:c.5979del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001127510.3:c.5979del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001127511.3:c.5925del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354895.2:c.5979del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354896.2:c.6033del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354897.2:c.6009del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354898.2:c.5904del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354899.2:c.5895del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354900.2:c.5856del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354901.2:c.5802del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354902.2:c.5706del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354903.2:c.5676del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354904.2:c.5601del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354905.2:c.5499del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354906.2:c.5130del - 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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606811 (1)
OMIM
Mus musculus strain C57BL/6J clone rp23-358m4, complete sequence
Mus musculus strain C57BL/6J clone rp23-358m4, complete sequence
gi|34365901|gnl|uoknor|rp23-358m4|g 40851.12|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001204204	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 21, 2022)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 9824584, 1316610, 27081525, 8381579, 22135120, 15311282, 17293347, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001204204

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 21, 2022)

germline

clinical testing

PubMed (8)
[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

Variable phenotype of familial adenomatous polyposis in pedigrees with 3' mutation in the APC gene.

Brensinger JD, Laken SJ, Luce MC, Powell SM, Vance GH, Ahnen DJ, Petersen GM, Hamilton SR, Giardiello FM.

Gut. 1998 Oct;43(4):548-52.

PubMed [citation]

PMID:: 9824584
PMCID:: PMC1727294

Germ-line mutations of the APC gene in 53 familial adenomatous polyposis patients.

Miyoshi Y, Ando H, Nagase H, Nishisho I, Horii A, Miki Y, Mori T, Utsunomiya J, Baba S, Petersen G, et al.

Proc Natl Acad Sci U S A. 1992 May 15;89(10):4452-6.

PubMed [citation]

PMID:: 1316610
PMCID:: PMC49100

See all PubMed Citations (8)

Details of each submission

From Invitae, SCV001204204.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

For these reasons, this variant has been classified as Pathogenic. A different truncation (p.Tyr2645Lysfs*14) that lies downstream of this variant has been determined to be pathogenic (PMID: 9824584, 1316610, 27081525, 8381579, 22135120, Invitae). This suggests that deletion of this region of the APC protein is causative of disease. This variant is expected to disrupt the EB1 and HDLG binding sites, which mediate interactions with the cytoskeleton (PMID: 15311282, 17293347). While functional studies have not been performed to directly test the effect on APC protein function, this suggests that disruption of the C-terminal portion of the protein is functionally important. ClinVar contains an entry for this variant (Variation ID: 838960). This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Asp1994Thrfs*50) in the APC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 850 amino acid(s) of the APC protein.

#	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: Jun 2, 2024

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