NM_000038.6(APC):c.350C>A (p.Ser117Ter) AND Familial adenomatous polyposis 1

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jan 27, 2024
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:: RCV002525784.12

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 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

Recent activity

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Homo sapiens protein phosphatase 6 regulatory subunit 3 (PPP6R3), transcript var...
Homo sapiens protein phosphatase 6 regulatory subunit 3 (PPP6R3), transcript variant 45, non-coding RNA
gi|1700447875|ref|NR_147969.2|

Nucleotide
Homo sapiens protein phosphatase 6 regulatory subunit 3 (PPP6R3), transcript var...
Homo sapiens protein phosphatase 6 regulatory subunit 3 (PPP6R3), transcript variant 42, non-coding RNA
gi|1700660455|ref|NR_147966.2|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000768277	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 27, 2024)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 17963004, 20685668, 11960572, 23159591, 28492532
SCV004045531	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Pathogenic (Apr 25, 2023)	unknown	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000768277

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 27, 2024)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV004045531

Myriad Genetics, Inc.

criteria provided, single submitter

(Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))

Pathogenic
(Apr 25, 2023)

unknown

clinical testing

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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutational screening of the APC gene in Chilean families with familial adenomatous polyposis: nine novel truncating mutations.

De la Fuente MK, Alvarez KP, Letelier AJ, Bellolio F, Acuña ML, León FS, Pinto E, Carvallo P, López-Köstner F.

Dis Colon Rectum. 2007 Dec;50(12):2142-8.

PubMed [citation]

PMID:: 17963004

Germline APC mutation spectrum derived from 863 genomic variations identified through a 15-year medical genetics service to French patients with FAP.

Lagarde A, Rouleau E, Ferrari A, Noguchi T, Qiu J, Briaux A, Bourdon V, Rémy V, Gaildrat P, Adélaïde J, Birnbaum D, Lidereau R, Sobol H, Olschwang S.

J Med Genet. 2010 Oct;47(10):721-2. doi: 10.1136/jmg.2010.078964. Epub 2010 Aug 3.

PubMed [citation]

PMID:: 20685668

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000768277.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change creates a premature translational stop signal (p.Ser117*) in the APC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in APC are known to be pathogenic (PMID: 17963004, 20685668). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with APC-related disease (PMID: 11960572, 23159591). ClinVar contains an entry for this variant (Variation ID: 418932). 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

From Myriad Genetics, Inc., SCV004045531.2

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

Description

This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 8, 2024

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