ClinVar Genomic variation as it relates to human health
NM_000038.6(APC):c.7589G>A (p.Arg2530Gln)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000038.6(APC):c.7589G>A (p.Arg2530Gln)
Variation ID: 133534 Accession: VCV000133534.18
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 5q22.2 5: 112843183 (GRCh38) [ NCBI UCSC ] 5: 112178880 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Jun 9, 2014 May 1, 2024 Dec 1, 2023 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_000038.6:c.7589G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000029.2:p.Arg2530Gln missense NM_001127510.3:c.7589G>A NP_001120982.1:p.Arg2530Gln missense NM_001127511.3:c.7535G>A NP_001120983.2:p.Arg2512Gln missense NM_001354895.2:c.7589G>A NP_001341824.1:p.Arg2530Gln missense NM_001354896.2:c.7643G>A NP_001341825.1:p.Arg2548Gln missense NM_001354897.2:c.7619G>A NP_001341826.1:p.Arg2540Gln missense NM_001354898.2:c.7514G>A NP_001341827.1:p.Arg2505Gln missense NM_001354899.2:c.7505G>A NP_001341828.1:p.Arg2502Gln missense NM_001354900.2:c.7466G>A NP_001341829.1:p.Arg2489Gln missense NM_001354901.2:c.7412G>A NP_001341830.1:p.Arg2471Gln missense NM_001354902.2:c.7316G>A NP_001341831.1:p.Arg2439Gln missense NM_001354903.2:c.7286G>A NP_001341832.1:p.Arg2429Gln missense NM_001354904.2:c.7211G>A NP_001341833.1:p.Arg2404Gln missense NM_001354905.2:c.7109G>A NP_001341834.1:p.Arg2370Gln missense NM_001354906.2:c.6740G>A NP_001341835.1:p.Arg2247Gln missense NC_000005.10:g.112843183G>A NC_000005.9:g.112178880G>A NG_008481.4:g.155663G>A LRG_130:g.155663G>A - Protein change
- R2512Q, R2530Q, R2439Q, R2489Q, R2247Q, R2505Q, R2548Q, R2404Q, R2471Q, R2502Q, R2370Q, R2429Q, R2540Q
- Other names
- -
- Canonical SPDI
- NC_000005.10:112843182:G:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
-
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.00000
Trans-Omics for Precision Medicine (TOPMed) 0.00000
Exome Aggregation Consortium (ExAC) 0.00001
The Genome Aggregation Database (gnomAD) 0.00001
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
---|---|---|---|---|---|---|
HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
APC | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
14630 | 14767 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
---|---|---|---|---|
Uncertain significance (2) |
criteria provided, single submitter
|
Mar 15, 2017 | RCV000120044.11 | |
Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
|
Feb 8, 2023 | RCV000222733.17 | |
Uncertain significance (1) |
criteria provided, single submitter
|
Dec 1, 2023 | RCV004562274.1 | |
Uncertain significance (1) |
criteria provided, single submitter
|
Mar 7, 2023 | RCV003997335.2 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
---|---|---|---|---|---|
Uncertain significance
(Jan 25, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000276417.7
First in ClinVar: May 29, 2016 Last updated: May 01, 2024 |
Comment:
The p.R2530Q variant (also known as c.7589G>A), located in coding exon 15 of the APC gene, results from a G to A substitution at nucleotide … (more)
The p.R2530Q variant (also known as c.7589G>A), located in coding exon 15 of the APC gene, results from a G to A substitution at nucleotide position 7589. The arginine at codon 2530 is replaced by glutamine, an amino acid with highly similar properties. This alteration has been reported in a cohort of 488 patients with stages I to III breast cancer who were tested with a 25-gene panel test (Tung N et al. J. Clin. Oncol., 2016 May;34:1460-8). This alteration was observed in a Japanese population cohort of 2049 individuals who underwent whole-genome sequencing (Yamaguchi-Kabata Y et al. J Hum Genet, 2018 Feb;63:213-230). This variant has also been identified in healthy cohorts without a known history of cancer (Bodian DL et al. PLoS One, 2014 Apr;9:e94554; Akcay IM et al. Int J Cancer, 2021 01;148:285-295).This amino acid position is highly conserved in available vertebrate species. In addition, in silico predictors for this gene do not accurately predict pathogenicity. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (less)
|
|
Uncertain significance
(Mar 15, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000600155.2
First in ClinVar: Jun 09, 2014 Last updated: Jan 01, 2022 |
|
|
Uncertain significance
(Feb 08, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000681880.5
First in ClinVar: Feb 19, 2018 Last updated: Feb 14, 2024 |
Comment:
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 … (more)
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. (less)
|
|
Uncertain significance
(Dec 01, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Familial adenomatous polyposis 1
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV001491555.4
First in ClinVar: Mar 07, 2021 Last updated: Feb 20, 2024 |
Comment:
This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 2530 of the APC protein (p.Arg2530Gln). … (more)
This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 2530 of the APC protein (p.Arg2530Gln). This variant is present in population databases (rs587778043, gnomAD 0.003%). This missense change has been observed in individual(s) with breast cancer (PMID: 26976419). ClinVar contains an entry for this variant (Variation ID: 133534). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt APC protein function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
|
|
Uncertain Significance
(Mar 07, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Classic or attenuated familial adenomatous polyposis
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
All of Us Research Program, National Institutes of Health
Accession: SCV004835699.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
|
Comment:
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 … (more)
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. (less)
Number of individuals with the variant: 2
|
|
not provided
(Sep 19, 2013)
|
no classification provided
Method: reference population
|
AllHighlyPenetrant
Affected status: unknown
Allele origin:
germline
|
ITMI
Accession: SCV000084178.1
First in ClinVar: Jun 09, 2014 Last updated: Jun 09, 2014
Comment:
Please see associated publication for description of ethnicities
|
Observation 1:
Ethnicity/Population group: Whole_cohort
Observation 2:
Ethnicity/Population group: African
Observation 3:
Ethnicity/Population group: African_European
Observation 4:
Ethnicity/Population group: Central_Asian
Observation 5:
Ethnicity/Population group: East_Asian
Observation 6:
Ethnicity/Population group: European
Observation 7:
Ethnicity/Population group: Hispanic
|
Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
Germline pathogenic variant spectrum in 25 cancer susceptibility genes in Turkish breast and colorectal cancer patients and elderly controls. | Akcay IM | International journal of cancer | 2021 | PMID: 32658311 |
Evaluation of reported pathogenic variants and their frequencies in a Japanese population based on a whole-genome reference panel of 2049 individuals. | Yamaguchi-Kabata Y | Journal of human genetics | 2018 | PMID: 29192238 |
Frequency of Germline Mutations in 25 Cancer Susceptibility Genes in a Sequential Series of Patients With Breast Cancer. | Tung N | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2016 | PMID: 26976419 |
Germline variation in cancer-susceptibility genes in a healthy, ancestrally diverse cohort: implications for individual genome sequencing. | Bodian DL | PloS one | 2014 | PMID: 24728327 |
Text-mined citations for rs587778043 ...
HelpRecord last updated Jun 30, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.