NM_000038.6(APC):c.3183_3187del (p.Lys1061_Gln1062insTer) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Mar 31, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000162768.17

Allele description [Variation Report for NM_000038.6(APC):c.3183_3187del (p.Lys1061_Gln1062insTer)]

NM_000038.6(APC):c.3183_3187del (p.Lys1061_Gln1062insTer)

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.3183_3187del (p.Lys1061_Gln1062insTer)

HGVS:

NC_000005.10:g.112838777_112838781del
NG_008481.4:g.151257_151261del
NM_000038.6:c.3183_3187delMANE SELECT
NM_001127510.3:c.3183_3187del
NM_001127511.3:c.3129_3133del
NM_001354895.2:c.3183_3187del
NM_001354896.2:c.3237_3241del
NM_001354897.2:c.3213_3217del
NM_001354898.2:c.3108_3112del
NM_001354899.2:c.3099_3103del
NM_001354900.2:c.3060_3064del
NM_001354901.2:c.3006_3010del
NM_001354902.2:c.2910_2914del
NM_001354903.2:c.2880_2884del
NM_001354904.2:c.2805_2809del
NM_001354905.2:c.2703_2707del
NM_001354906.2:c.2334_2338del
NM_001407446.1:c.3267_3271delACAAA
NM_001407447.1:c.3237_3241delACAAA
NM_001407448.1:c.3237_3241delACAAA
NM_001407449.1:c.3237_3241delACAAA
NM_001407450.1:c.3183_3187delACAAA
NM_001407451.1:c.3162_3166delACAAA
NM_001407452.1:c.3153_3157delACAAA
NM_001407453.1:c.3006_3010delACAAA
NM_001407454.1:c.2934_2938delACAAA
NM_001407455.1:c.2934_2938delACAAA
NM_001407456.1:c.2934_2938delACAAA
NM_001407457.1:c.2934_2938delACAAA
NM_001407458.1:c.2880_2884delACAAA
NM_001407459.1:c.2880_2884delACAAA
NM_001407460.1:c.2880_2884delACAAA
NM_001407467.1:c.2796_2800delACAAA
NM_001407469.1:c.2796_2800delACAAA
NM_001407470.1:c.2334_2338delACAAA
NM_001407471.1:c.2031_2035delACAAA
NM_001407472.1:c.2031_2035delACAAA
NP_000029.2:p.Gln1062Terfs
NP_000029.2:p.Lys1061_Gln1062insTer
NP_001120982.1:p.Gln1062Terfs
NP_001120982.1:p.Lys1061_Gln1062insTer
NP_001120983.1:p.Gln1062Terfs
NP_001120983.2:p.Lys1043_Gln1044insTer
NP_001341824.1:p.Lys1061_Gln1062insTer
NP_001341825.1:p.Lys1079_Gln1080insTer
NP_001341826.1:p.Lys1071_Gln1072insTer
NP_001341827.1:p.Lys1036_Gln1037insTer
NP_001341828.1:p.Lys1033_Gln1034insTer
NP_001341829.1:p.Lys1020_Gln1021insTer
NP_001341830.1:p.Lys1002_Gln1003insTer
NP_001341831.1:p.Lys970_Gln971insTer
NP_001341832.1:p.Lys960_Gln961insTer
NP_001341833.1:p.Lys935_Gln936insTer
NP_001341834.1:p.Lys901_Gln902insTer
NP_001341835.1:p.Lys778_Gln779insTer
NP_001394375.1:p.Gln1090Terfs
NP_001394376.1:p.Gln1080Terfs
NP_001394377.1:p.Gln1080Terfs
NP_001394378.1:p.Gln1080Terfs
NP_001394379.1:p.Gln1062Terfs
NP_001394380.1:p.Gln1055Terfs
NP_001394381.1:p.Gln1052Terfs
NP_001394382.1:p.Gln1003Terfs
NP_001394383.1:p.Gln979Terfs
NP_001394384.1:p.Gln979Terfs
NP_001394385.1:p.Gln979Terfs
NP_001394386.1:p.Gln979Terfs
NP_001394387.1:p.Gln961Terfs
NP_001394388.1:p.Gln961Terfs
NP_001394389.1:p.Gln961Terfs
NP_001394396.1:p.Gln933Terfs
NP_001394398.1:p.Gln933Terfs
NP_001394399.1:p.Gln779Terfs
NP_001394400.1:p.Gln678Terfs
NP_001394401.1:p.Gln678Terfs
LRG_130t1:c.3183_3187del
LRG_130t2:c.3183_3187del
LRG_130t3:c.3183_3187del
LRG_130:g.151257_151261del
LRG_130p1:p.Gln1062Terfs
LRG_130p2:p.Gln1062Terfs
LRG_130p3:p.Gln1062Terfs
NC_000005.9:g.112174471_112174475del
NC_000005.9:g.112174474_112174478del
NM_000038.4:c.3183_3187delACAAA
NM_000038.5:c.3183_3187delACAAA
NM_000038.6:c.3183_3187delACAAAMANE SELECT
NM_001127510.1:c.3183_3187delACAAA
NM_001127511.1:c.3183_3187delACAAA
NR_176365.1:n.3018_3022delACAAA
NR_176366.1:n.3437_3441delACAAA
p.Gln1062*
p.Q1062*

Links:

Genetic Testing Registry (GTR): GTR000330983; dbSNP: rs587779352

NCBI 1000 Genomes Browser:

rs587779352

Molecular consequence:

NM_000038.6:c.3183_3187del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001127510.3:c.3183_3187del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001127511.3:c.3129_3133del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354895.2:c.3183_3187del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354896.2:c.3237_3241del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354897.2:c.3213_3217del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354898.2:c.3108_3112del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354899.2:c.3099_3103del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354900.2:c.3060_3064del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354901.2:c.3006_3010del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354902.2:c.2910_2914del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354903.2:c.2880_2884del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354904.2:c.2805_2809del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354905.2:c.2703_2707del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354906.2:c.2334_2338del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407446.1:c.3267_3271delACAAA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407447.1:c.3237_3241delACAAA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407448.1:c.3237_3241delACAAA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407449.1:c.3237_3241delACAAA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407450.1:c.3183_3187delACAAA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407451.1:c.3162_3166delACAAA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407452.1:c.3153_3157delACAAA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407453.1:c.3006_3010delACAAA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407454.1:c.2934_2938delACAAA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407455.1:c.2934_2938delACAAA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407456.1:c.2934_2938delACAAA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407457.1:c.2934_2938delACAAA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407458.1:c.2880_2884delACAAA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407459.1:c.2880_2884delACAAA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407460.1:c.2880_2884delACAAA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407467.1:c.2796_2800delACAAA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407469.1:c.2796_2800delACAAA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407470.1:c.2334_2338delACAAA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407471.1:c.2031_2035delACAAA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407472.1:c.2031_2035delACAAA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407446.1:c.3267_3271delACAAA - nonsense - [Sequence Ontology: SO:0001587]
NM_001407447.1:c.3237_3241delACAAA - nonsense - [Sequence Ontology: SO:0001587]
NM_001407448.1:c.3237_3241delACAAA - nonsense - [Sequence Ontology: SO:0001587]
NM_001407449.1:c.3237_3241delACAAA - nonsense - [Sequence Ontology: SO:0001587]
NM_001407450.1:c.3183_3187delACAAA - nonsense - [Sequence Ontology: SO:0001587]
NM_001407451.1:c.3162_3166delACAAA - nonsense - [Sequence Ontology: SO:0001587]
NM_001407452.1:c.3153_3157delACAAA - nonsense - [Sequence Ontology: SO:0001587]
NM_001407453.1:c.3006_3010delACAAA - nonsense - [Sequence Ontology: SO:0001587]
NM_001407454.1:c.2934_2938delACAAA - nonsense - [Sequence Ontology: SO:0001587]
NM_001407455.1:c.2934_2938delACAAA - nonsense - [Sequence Ontology: SO:0001587]
NM_001407456.1:c.2934_2938delACAAA - nonsense - [Sequence Ontology: SO:0001587]
NM_001407457.1:c.2934_2938delACAAA - nonsense - [Sequence Ontology: SO:0001587]
NM_001407458.1:c.2880_2884delACAAA - nonsense - [Sequence Ontology: SO:0001587]
NM_001407459.1:c.2880_2884delACAAA - nonsense - [Sequence Ontology: SO:0001587]
NM_001407460.1:c.2880_2884delACAAA - nonsense - [Sequence Ontology: SO:0001587]
NM_001407467.1:c.2796_2800delACAAA - nonsense - [Sequence Ontology: SO:0001587]
NM_001407469.1:c.2796_2800delACAAA - nonsense - [Sequence Ontology: SO:0001587]
NM_001407470.1:c.2334_2338delACAAA - nonsense - [Sequence Ontology: SO:0001587]
NM_001407471.1:c.2031_2035delACAAA - nonsense - [Sequence Ontology: SO:0001587]
NM_001407472.1:c.2031_2035delACAAA - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000213245	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Mar 31, 2022)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 10083733, 15771908, 16088911, 19029688, 20649969, 20924072, 23159591, 26446593, 26840078 Citation Link,
SCV000905975	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 15, 2020)	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

SCV000213245

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Mar 31, 2022)

germline

clinical testing

PubMed (9)
[See all records that cite these PMIDs]

Citation Link,

SCV000905975

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jan 15, 2020)

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

Germline mutations of the APC gene in Korean familial adenomatous polyposis patients.

Won YJ, Park KJ, Kwon HJ, Lee JH, Kim JH, Kim YJ, Chun SH, Han HJ, Park JG.

J Hum Genet. 1999;44(2):103-8.

PubMed [citation]

PMID:: 10083733

Founder mutation in familial adenomatous polyposis (FAP) in the Balearic Islands.

González S, Blanco I, Campos O, Julià M, Reyes J, Llompart A, Cabeza E, Germà JR, Obrador A, Capellá G.

Cancer Genet Cytogenet. 2005 Apr 1;158(1):70-4.

PubMed [citation]

PMID:: 15771908

See all PubMed Citations (10)

Details of each submission

From Ambry Genetics, SCV000213245.9

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (9)

Description

The c.3183_3187delACAAA pathogenic mutation (also known as p.Q1062*), located in coding exon 15 of the APC gene, results from a deletion of 5 nucleotides at nucleotide positions 3183 to 3187. This changes the amino acid from a glutamine to a stop codon within coding exon 15. This mutation has been identified in numerous individuals and families from a variety of ethnic backgrounds with classic familial adenomatous polyposis (FAP), including some individuals with extra colonic manifestations including desmoid tumors, gastrointestinal cancers, papillary thyroid cancer, congenital hypertrophy of the retinal pigment epithelium (CHRPE), and epidermal cysts (Miyoshi Y et al. Proc. Natl. Acad. Sci. U.S.A. 1992 May;89:4452-6; Won YJ et al. J. Hum. Genet. 1999;44:103-8; González S et al. Cancer Genet. Cytogenet. 2005 Apr;158:70-4; Kim DW et al. Hum. Mutat. 2005 Sep;26:281; Friedl W & Aretz S. Hered. Cancer Clin. Pract. 2005 Sep;3:95-114; Plawski A & Slomski R. J. Appl. Genet. 2008;49:407-14; Fostira F et al. BMC Cancer. 2010 Jul;10:389; Rivera B et al. Ann. Oncol. 2011 Apr;22:903-9; Kerr SE et al. J. Mol. Diagn. 2013 Jan;15:31-43; Papp J et al. Fam. Cancer. 2016 Jan;15(1):85-97; Dahl NA et al. J. Pediatr. Hematol. Oncol. 2016 07;38(5):e154-7). Of note, this alteration is also described as a truncation at codon 1061 or codon 1060, and as c.3221_3225delACAAA in the literature. In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation. As such, this alteration is interpreted as a disease-causing mutation.

#	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

From Color Diagnostics, LLC DBA Color Health, SCV000905975.3

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

Description

This variant deletes 5 nucleotides in exon 16 of the APC gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been identified in 1/250490 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of APC function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is 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: May 19, 2024

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