NM_000038.6(APC):c.3183_3187del (p.Lys1061_Gln1062insTer) AND Familial multiple polyposis syndrome
- Germline classification:
- Pathogenic (2 submissions)
- Last evaluated:
- Oct 28, 2019
- Review status:
- 2 stars out of maximum of 4 starscriteria provided, multiple submitters, no conflicts
- Somatic classification
of clinical impact: - None
- Review status:
- (0/4) 0 stars out of maximum of 4 starsno assertion criteria provided
- Somatic classification
of oncogenicity: - None
- Review status:
- (0/4) 0 stars out of maximum of 4 starsno assertion criteria provided
- Record status:
- current
- Accession:
- RCV000502016.12
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*
This HGVS expression did not pass validation- 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:
- 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
Assertion and evidence details
Submission Accession | Submitter | Review Status (Assertion method) | Clinical Significance (Last evaluated) | Origin | Method | Citations |
---|---|---|---|---|---|---|
SCV000694026 | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) | Pathogenic (Oct 28, 2019) | germline | clinical testing | |
SCV000781075 | Center for Human Genetics, Inc, Center for Human Genetics, Inc | criteria provided, single submitter (ACMG Guidelines, 2015) | Pathogenic (Nov 1, 2016) | germline | clinical testing |
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 |
not provided | germline | yes | not provided | not provided | not provided | not provided | not provided | clinical testing |
Citations
PubMed
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.
- PMID:
- 1316610
- PMCID:
- PMC49100
Contribution of APC and MUTYH mutations to familial adenomatous polyposis susceptibility in Hungary.
Papp J, Kovacs ME, Matrai Z, Orosz E, Kásler M, Børresen-Dale AL, Olah E.
Fam Cancer. 2016 Jan;15(1):85-97. doi: 10.1007/s10689-015-9845-5.
- PMID:
- 26446593
- PMCID:
- PMC4698287
Details of each submission
From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000694026.2
# | Ethnicity | Individuals | Chromosomes Tested | Family History | Method | Citations |
---|---|---|---|---|---|---|
1 | not provided | not provided | not provided | not provided | clinical testing | PubMed (3) |
Description
Variant summary: APC c.3183_3187delACAAA (p.Gln1062X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 4e-06 in 250490 control chromosomes (gnomAD). c.3183_3187delACAAA has been reported in the literature in multiple individuals affected with Familial Adenomatous Polyposis and colorectal cancer (Inra_2015, Miyoshi_1992, Papp_2016). These data indicate that the variant is very likely to be associated with disease. 11 ClinVar submitters (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was 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 |
From Center for Human Genetics, Inc, Center for Human Genetics, Inc, SCV000781075.1
# | Ethnicity | Individuals | Chromosomes Tested | Family History | Method | Citations |
---|---|---|---|---|---|---|
1 | not provided | not provided | not provided | not provided | clinical testing | PubMed (1) |
# | Sample | Method | Observation | |||||||
---|---|---|---|---|---|---|---|---|---|---|
Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences | |
1 | germline | yes | not provided | not provided | not provided | not provided | not provided | not provided | not provided |
Last Updated: May 12, 2024