NM_000038.6(APC):c.350C>A (p.Ser117Ter) AND Familial multiple polyposis syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 10, 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:: RCV001824795.9

Allele description [Variation Report for NM_000038.6(APC):c.350C>A (p.Ser117Ter)]

NM_000038.6(APC):c.350C>A (p.Ser117Ter)

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.350C>A (p.Ser117Ter)

HGVS:

NC_000005.10:g.112767318C>A
NG_008481.4:g.79798C>A
NM_000038.6:c.350C>AMANE SELECT
NM_001127510.3:c.350C>A
NM_001127511.3:c.380C>A
NM_001354895.2:c.350C>A
NM_001354896.2:c.350C>A
NM_001354897.2:c.380C>A
NM_001354898.2:c.275C>A
NM_001354899.2:c.350C>A
NM_001354900.2:c.173C>A
NM_001354901.2:c.173C>A
NM_001354902.2:c.380C>A
NM_001354903.2:c.350C>A
NM_001354904.2:c.275C>A
NM_001354905.2:c.173C>A
NM_001354906.2:c.-686C>A
NP_000029.2:p.Ser117Ter
NP_001120982.1:p.Ser117Ter
NP_001120983.2:p.Ser127Ter
NP_001341824.1:p.Ser117Ter
NP_001341825.1:p.Ser117Ter
NP_001341826.1:p.Ser127Ter
NP_001341827.1:p.Ser92Ter
NP_001341828.1:p.Ser117Ter
NP_001341829.1:p.Ser58Ter
NP_001341830.1:p.Ser58Ter
NP_001341831.1:p.Ser127Ter
NP_001341832.1:p.Ser117Ter
NP_001341833.1:p.Ser92Ter
NP_001341834.1:p.Ser58Ter
LRG_130:g.79798C>A
NC_000005.9:g.112103015C>A
NM_000038.5:c.350C>A

Protein change:

S117*

Links:

dbSNP: rs1064793535

NCBI 1000 Genomes Browser:

rs1064793535

Molecular consequence:

NM_001354906.2:c.-686C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000038.6:c.350C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001127510.3:c.350C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001127511.3:c.380C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001354895.2:c.350C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001354896.2:c.350C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001354897.2:c.380C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001354898.2:c.275C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001354899.2:c.350C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001354900.2:c.173C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001354901.2:c.173C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001354902.2:c.380C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001354903.2:c.350C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001354904.2:c.275C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001354905.2:c.173C>A - 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

Recent activity

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regulator of nonsense transcripts 1 isoform X3 [Homo sapiens]
regulator of nonsense transcripts 1 isoform X3 [Homo sapiens]
gi|2217322339|ref|XP_047295147.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002074167	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Jan 10, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 23159591, 11960572, 33788735 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002074167

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Jan 10, 2022)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

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

APC germline mutations in individuals being evaluated for familial adenomatous polyposis: a review of the Mayo Clinic experience with 1591 consecutive tests.

Kerr SE, Thomas CB, Thibodeau SN, Ferber MJ, Halling KC.

J Mol Diagn. 2013 Jan;15(1):31-43. doi: 10.1016/j.jmoldx.2012.07.005. Epub 2012 Nov 14. Review.

PubMed [citation]

PMID:: 23159591

Detection of sequence variations in the adenomatous polyposis coli (APC) gene using denaturing high-performance liquid chromatography.

Wu G, Wu W, Hegde M, Fawkner M, Chong B, Love D, Su LK, Lynch P, Snow K, Richards CS.

Genet Test. 2001 Winter;5(4):281-90.

PubMed [citation]

PMID:: 11960572

See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002074167.1

#	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.350C>A (p.Ser117X) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251476 control chromosomes (gnomAD). c.350C>A has been reported in the literature in individuals affected with Familial Adenomatous Polyposis (examples: Wu_2001, Kerr_2013 and Findlen_2021). These data indicate that the variant is associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified 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

Last Updated: Nov 3, 2024

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