ClinVar Genomic variation as it relates to human health
NM_000038.6(APC):c.5392A>G (p.Asn1798Asp)
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.
Uncertain significance(5); Benign(1); Likely benign(5)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000038.6(APC):c.5392A>G (p.Asn1798Asp)
Variation ID: 41532 Accession: VCV000041532.28
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 5q22.2 5: 112840986 (GRCh38) [ NCBI UCSC ] 5: 112176683 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Apr 12, 2013 Feb 14, 2024 Jan 27, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000038.6:c.5392A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000029.2:p.Asn1798Asp missense NM_001127510.3:c.5392A>G NP_001120982.1:p.Asn1798Asp missense NM_001127511.3:c.5338A>G NP_001120983.2:p.Asn1780Asp missense NM_001354895.2:c.5392A>G NP_001341824.1:p.Asn1798Asp missense NM_001354896.2:c.5446A>G NP_001341825.1:p.Asn1816Asp missense NM_001354897.2:c.5422A>G NP_001341826.1:p.Asn1808Asp missense NM_001354898.2:c.5317A>G NP_001341827.1:p.Asn1773Asp missense NM_001354899.2:c.5308A>G NP_001341828.1:p.Asn1770Asp missense NM_001354900.2:c.5269A>G NP_001341829.1:p.Asn1757Asp missense NM_001354901.2:c.5215A>G NP_001341830.1:p.Asn1739Asp missense NM_001354902.2:c.5119A>G NP_001341831.1:p.Asn1707Asp missense NM_001354903.2:c.5089A>G NP_001341832.1:p.Asn1697Asp missense NM_001354904.2:c.5014A>G NP_001341833.1:p.Asn1672Asp missense NM_001354905.2:c.4912A>G NP_001341834.1:p.Asn1638Asp missense NM_001354906.2:c.4543A>G NP_001341835.1:p.Asn1515Asp missense NC_000005.10:g.112840986A>G NC_000005.9:g.112176683A>G NG_008481.4:g.153466A>G LRG_130:g.153466A>G LRG_130t1:c.5392A>G - Protein change
- N1798D, N1780D, N1707D, N1739D, N1770D, N1773D, N1808D, N1515D, N1816D, N1638D, N1672D, N1697D, N1757D
- Other names
- p.N1798D:AAT>GAT
- Canonical SPDI
- NC_000005.10:112840985:A:G
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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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.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00012
The Genome Aggregation Database (gnomAD), exomes 0.00004
Exome Aggregation Consortium (ExAC) 0.00007
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
Trans-Omics for Precision Medicine (TOPMed) 0.00014
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 | ||
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HI score
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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. |
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APC | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
14091 | 14225 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
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Dec 3, 2022 | RCV000034417.12 | |
Likely benign (2) |
criteria provided, multiple submitters, no conflicts
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Sep 20, 2021 | RCV000035077.22 | |
Uncertain significance (2) |
criteria provided, conflicting classifications
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Jul 2, 2018 | RCV000167996.21 | |
Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
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Mar 8, 2023 | RCV000491791.18 | |
Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
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Jan 27, 2024 | RCV003315549.9 |
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. |
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Likely benign
(May 02, 2019)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000058717.6
First in ClinVar: May 03, 2013 Last updated: Jul 03, 2020 |
Comment:
The p.Asn1798Asp variant in APC is classified as likely benign because it has been identified in 0.053% (13/24620) of African chromosomes by gnomAD (http://gnomad.broadinstitute.org), and … (more)
The p.Asn1798Asp variant in APC is classified as likely benign because it has been identified in 0.053% (13/24620) of African chromosomes by gnomAD (http://gnomad.broadinstitute.org), and computational tools suggest that this variant may not impact the protein. This variant has been reported in ClinVar (Variation ID 41532) and has been observed in 1/403 individuals with atherosclerosis and in 1 South African individual with colorectal cancer (Johnston 2012, Felix 2003); however its allele frequency of 0.053% is higher than expected for a pathogenic APC variant associated with familial adenomatous polyposis, which has an estimated prevalence of 1/7000. ACMG/AMP criteria applied: BS1, BP4. (less)
Number of individuals with the variant: 1
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Uncertain significance
(Jul 02, 2018)
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criteria provided, single submitter
Method: clinical testing
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Familial adenomatous polyposis 1
Affected status: unknown
Allele origin:
unknown
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Mendelics
Accession: SCV000838133.2
First in ClinVar: Oct 10, 2018 Last updated: Dec 11, 2022 |
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Uncertain significance
(Mar 01, 2016)
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criteria provided, single submitter
Method: clinical testing
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Familial adenomatous polyposis 1
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000488327.2
First in ClinVar: Oct 11, 2015 Last updated: Dec 24, 2022 |
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Likely benign
(Dec 03, 2022)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000600115.4
First in ClinVar: Sep 28, 2017 Last updated: Jan 06, 2024 |
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Likely benign
(Jan 27, 2024)
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criteria provided, single submitter
Method: clinical testing
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Familial adenomatous polyposis 1
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000218647.11
First in ClinVar: Mar 29, 2015 Last updated: Feb 14, 2024 |
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Uncertain significance
(Jun 25, 2018)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000209532.12
First in ClinVar: Feb 24, 2015 Last updated: Apr 17, 2019 |
Comment:
This variant is denoted APC c.5392A>G at the cDNA level, p.Asn1798Asp (N1798D) at the protein level, and results in the change of an Asparagine to … (more)
This variant is denoted APC c.5392A>G at the cDNA level, p.Asn1798Asp (N1798D) at the protein level, and results in the change of an Asparagine to an Aspartic Acid (AAT>GAT). This variant was observed in 1/430 individuals with atherosclerosis, with no specific information about cancer history (Johnston 2012). APC Asn1798Asp was not observed at a significant allele frequency in large population cohorts (Lek 2016). APC Asn1798Asp is located in the beta-catenin binding domain and the SAMP repeats/axin binding domain (Azzopardi 2008). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether APC Asn1798Asp is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. (less)
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Likely benign
(Jul 21, 2020)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Color Diagnostics, LLC DBA Color Health
Accession: SCV000681736.4
First in ClinVar: Feb 19, 2018 Last updated: Jun 19, 2021 |
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Likely benign
(Sep 20, 2021)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001361423.2
First in ClinVar: Jun 22, 2020 Last updated: Oct 30, 2021 |
Comment:
Variant summary: APC c.5392A>G (p.Asn1798Asp) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign … (more)
Variant summary: APC c.5392A>G (p.Asn1798Asp) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 5.3e-05 in 280972 control chromosomes, predominantly at a frequency of 0.00053 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 7-fold of the estimated maximal expected allele frequency for a pathogenic variant in APC causing Familial Adenomatous Polyposis phenotype (7.1e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. The variant, c.5392A>G, has been reported in the literature in individuals affected with atherosclerosis, pediatric astrocytoma, and breast cancer (Johnston_2012, Muskens_2020, Sandoval_2021). These reports do not provide unequivocal conclusions about association of the variant with Familial Adenomatous Polyposis. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Eight other submitters have provided clinical-significance assessments for this variant in ClinVar after 2014 without evidence for independent evaluation, and classified the variant as VUS (n=6) or likely benign (n=2). Based on the evidence outlined above, the variant was classified as likely benign. (less)
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Uncertain significance
(Nov 23, 2021)
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criteria provided, single submitter
Method: curation
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Sema4, Sema4
Accession: SCV002535641.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022 |
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Benign
(Mar 08, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000579863.6
First in ClinVar: Jun 25, 2017 Last updated: Apr 15, 2023 |
Comment:
This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA … (more)
This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
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Uncertain significance
(Feb 22, 2023)
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criteria provided, single submitter
Method: clinical testing
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Familial adenomatous polyposis 1
Affected status: unknown
Allele origin:
unknown
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Myriad Genetics, Inc.
Accession: SCV004018807.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023 |
Comment:
This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.
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variant of unknown significance
(Jul 13, 2012)
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no assertion criteria provided
Method: research
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not provided
Affected status: no
Allele origin:
germline
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Biesecker Lab/Clinical Genomics Section, National Institutes of Health
Study: ClinSeq
Accession: SCV000043132.1 First in ClinVar: Apr 12, 2013 Last updated: Apr 12, 2013 |
Comment:
Converted during submission to Uncertain significance.
Number of individuals with the variant: 1
Comment on evidence:
The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:22703879 for … (more)
The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:22703879 for details. (less)
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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 |
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Germline molecular data in hereditary breast cancer in Brazil: Lessons from a large single-center analysis. | Sandoval RL | PloS one | 2021 | PMID: 33606809 |
Germline cancer predisposition variants and pediatric glioma: a population-based study in California. | Muskens IS | Neuro-oncology | 2020 | PMID: 31970404 |
Actionable Genes, Core Databases, and Locus-Specific Databases. | Pinard A | Human mutation | 2016 | PMID: 27600092 |
Secondary variants in individuals undergoing exome sequencing: screening of 572 individuals identifies high-penetrance mutations in cancer-susceptibility genes. | Johnston JJ | American journal of human genetics | 2012 | PMID: 22703879 |
Text-mined citations for rs200794097 ...
HelpRecord last updated Apr 20, 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.