NM_000038.6(APC):c.7709C>G (p.Ser2570Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Apr 15, 2020
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:: RCV000772432.7

Allele description [Variation Report for NM_000038.6(APC):c.7709C>G (p.Ser2570Ter)]

NM_000038.6(APC):c.7709C>G (p.Ser2570Ter)

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.7709C>G (p.Ser2570Ter)

HGVS:

NC_000005.10:g.112843303C>G
NG_008481.4:g.155783C>G
NM_000038.6:c.7709C>GMANE SELECT
NM_001127510.3:c.7709C>G
NM_001127511.3:c.7655C>G
NM_001354895.2:c.7709C>G
NM_001354896.2:c.7763C>G
NM_001354897.2:c.7739C>G
NM_001354898.2:c.7634C>G
NM_001354899.2:c.7625C>G
NM_001354900.2:c.7586C>G
NM_001354901.2:c.7532C>G
NM_001354902.2:c.7436C>G
NM_001354903.2:c.7406C>G
NM_001354904.2:c.7331C>G
NM_001354905.2:c.7229C>G
NM_001354906.2:c.6860C>G
NP_000029.2:p.Ser2570Ter
NP_001120982.1:p.Ser2570Ter
NP_001120983.2:p.Ser2552Ter
NP_001341824.1:p.Ser2570Ter
NP_001341825.1:p.Ser2588Ter
NP_001341826.1:p.Ser2580Ter
NP_001341827.1:p.Ser2545Ter
NP_001341828.1:p.Ser2542Ter
NP_001341829.1:p.Ser2529Ter
NP_001341830.1:p.Ser2511Ter
NP_001341831.1:p.Ser2479Ter
NP_001341832.1:p.Ser2469Ter
NP_001341833.1:p.Ser2444Ter
NP_001341834.1:p.Ser2410Ter
NP_001341835.1:p.Ser2287Ter
LRG_130:g.155783C>G
NC_000005.9:g.112179000C>G
NM_000038.5:c.7709C>G

Protein change:

S2287*

Links:

dbSNP: rs1561617778

NCBI 1000 Genomes Browser:

rs1561617778

Molecular consequence:

NM_000038.6:c.7709C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001127510.3:c.7709C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001127511.3:c.7655C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001354895.2:c.7709C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001354896.2:c.7763C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001354897.2:c.7739C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001354898.2:c.7634C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001354899.2:c.7625C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001354900.2:c.7586C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001354901.2:c.7532C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001354902.2:c.7436C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001354903.2:c.7406C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001354904.2:c.7331C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001354905.2:c.7229C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001354906.2:c.6860C>G - 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

Recent activity

Clear Turn Off Turn On

C-terminal-binding protein 1 isoform X7 [Pyrgilauda ruficollis]
C-terminal-binding protein 1 isoform X7 [Pyrgilauda ruficollis]
gi|2032732266|ref|XP_041325110.1|

Protein
Homo sapiens glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase (...
Homo sapiens glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase (GNE), transcript variant 4, mRNA
gi|1677537874|ref|NM_001190383.3|

Nucleotide

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000905610	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 15, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001189176	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Jan 25, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000905610

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Apr 15, 2020)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV001189176

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Jan 25, 2018)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

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

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV000905610.3

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

Description

This variant changes 1 nucleotide, creating a premature translation stop signal in the last coding exon of the APC gene. While this mutant transcript is predicted to escape nonsense-mediated decay, it is expected to delete 274 amino acids at the C-terminal end of the APC protein and disrupt the EB1 and HDLG binding domains. This variant has been reported in an individual affected with familial adenomatous polyposis (PMID: 23159591). This variant has not been identified 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

From Ambry Genetics, SCV001189176.4

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

Description

The p.S2570* pathogenic mutation (also known as c.7709C>G), located in coding exon 15 of the APC gene, results from a C to G substitution at nucleotide position 7709. This changes the amino acid from a serine to a stop codon within coding exon 15. In a large (n=1591) series of patients referred for APC testing, this alteration was detected in 1 individual and interpreted as pathogenic (Kerr SE et al. J Mol Diagn, 2013 Jan;15:31-43). In addition to the published data, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. 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

Last Updated: May 1, 2024

ClinVar

Relating variation to medicine