NM_000038.6(APC):c.7589G>A (p.Arg2530Gln) AND Classic or attenuated familial adenomatous polyposis

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 7, 2023
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:: RCV003997335.2

Allele description [Variation Report for NM_000038.6(APC):c.7589G>A (p.Arg2530Gln)]

NM_000038.6(APC):c.7589G>A (p.Arg2530Gln)

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.7589G>A (p.Arg2530Gln)

HGVS:

NC_000005.10:g.112843183G>A
NG_008481.4:g.155663G>A
NM_000038.6:c.7589G>AMANE SELECT
NM_001127510.3:c.7589G>A
NM_001127511.3:c.7535G>A
NM_001354895.2:c.7589G>A
NM_001354896.2:c.7643G>A
NM_001354897.2:c.7619G>A
NM_001354898.2:c.7514G>A
NM_001354899.2:c.7505G>A
NM_001354900.2:c.7466G>A
NM_001354901.2:c.7412G>A
NM_001354902.2:c.7316G>A
NM_001354903.2:c.7286G>A
NM_001354904.2:c.7211G>A
NM_001354905.2:c.7109G>A
NM_001354906.2:c.6740G>A
NP_000029.2:p.Arg2530Gln
NP_001120982.1:p.Arg2530Gln
NP_001120983.2:p.Arg2512Gln
NP_001341824.1:p.Arg2530Gln
NP_001341825.1:p.Arg2548Gln
NP_001341826.1:p.Arg2540Gln
NP_001341827.1:p.Arg2505Gln
NP_001341828.1:p.Arg2502Gln
NP_001341829.1:p.Arg2489Gln
NP_001341830.1:p.Arg2471Gln
NP_001341831.1:p.Arg2439Gln
NP_001341832.1:p.Arg2429Gln
NP_001341833.1:p.Arg2404Gln
NP_001341834.1:p.Arg2370Gln
NP_001341835.1:p.Arg2247Gln
LRG_130:g.155663G>A
NC_000005.9:g.112178880G>A
NM_000038.5:c.7589G>A

Protein change:

R2247Q

Links:

dbSNP: rs587778043

NCBI 1000 Genomes Browser:

rs587778043

Molecular consequence:

NM_000038.6:c.7589G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001127510.3:c.7589G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001127511.3:c.7535G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354895.2:c.7589G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354896.2:c.7643G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354897.2:c.7619G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354898.2:c.7514G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354899.2:c.7505G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354900.2:c.7466G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354901.2:c.7412G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354902.2:c.7316G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354903.2:c.7286G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354904.2:c.7211G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354905.2:c.7109G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354906.2:c.6740G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Classic or attenuated familial adenomatous polyposis
Identifiers:: MONDO: MONDO:0021057; MedGen: CN372698

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004835699	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain Significance (Mar 7, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 24728327, 26976419, 29192238, 32658311, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004835699

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain Significance
(Mar 7, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	2	not provided	not provided	108544	not provided	clinical testing

Citations

PubMed

Germline variation in cancer-susceptibility genes in a healthy, ancestrally diverse cohort: implications for individual genome sequencing.

Bodian DL, McCutcheon JN, Kothiyal P, Huddleston KC, Iyer RK, Vockley JG, Niederhuber JE.

PLoS One. 2014;9(4):e94554. doi: 10.1371/journal.pone.0094554.

PubMed [citation]

PMID:: 24728327
PMCID:: PMC3984285

Frequency of Germline Mutations in 25 Cancer Susceptibility Genes in a Sequential Series of Patients With Breast Cancer.

Tung N, Lin NU, Kidd J, Allen BA, Singh N, Wenstrup RJ, Hartman AR, Winer EP, Garber JE.

J Clin Oncol. 2016 May 1;34(13):1460-8. doi: 10.1200/JCO.2015.65.0747. Epub 2016 Mar 14.

PubMed [citation]

PMID:: 26976419
PMCID:: PMC4872307

See all PubMed Citations (5)

Details of each submission

From All of Us Research Program, National Institutes of Health, SCV004835699.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	PubMed (5)

Description

This missense variant replaces arginine with glutamine at codon 2530 of the APC protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on protein structure and function. Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has been reported in an individual affected with breast cancer (PMID: 26976419), but also in healthy control individuals (PMID: 24728327, 29192238, 32658311). This variant has also been identified in 1/250692 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	108544	not provided	not provided		2	not provided	not provided	not provided

Last Updated: Sep 16, 2024

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