Variant summary: The variant, APC c.6473C>G (p.Pro2158Arg) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 5e-05 in 278626 control chromosomes (gnomAD and Azzopardi_2008). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. The variant, c.6473C>G has been reported in the literature in individuals affected with colorectal cancer, familial adenomatous polyposis, and breast cancer (Azzopardi_2008, Pearlman_2016, Zhang_2015). However, 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. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
ClinVar Genomic variation as it relates to human health
NM_000038.6(APC):c.6473C>G (p.Pro2158Arg)
Germline
Classification
Help
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.
(12)
Help
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.
Conflicting classifications of pathogenicity
Uncertain significance(8); Likely benign(2)
Uncertain significance(8); Likely benign(2)
12
criteria provided, conflicting classifications
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000038.6(APC):c.6473C>G (p.Pro2158Arg)
Variation ID: 127313 Accession: VCV000127313.34
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 5q22.2 5: 112842067 (GRCh38) [ NCBI UCSC ] 5: 112177764 (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 Oct 19, 2014 Oct 8, 2024 Feb 5, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000038.6:c.6473C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000029.2:p.Pro2158Arg missense NM_001127510.3:c.6473C>G NP_001120982.1:p.Pro2158Arg missense NM_001127511.3:c.6419C>G NP_001120983.2:p.Pro2140Arg missense NM_001354895.2:c.6473C>G NP_001341824.1:p.Pro2158Arg missense NM_001354896.2:c.6527C>G NP_001341825.1:p.Pro2176Arg missense NM_001354897.2:c.6503C>G NP_001341826.1:p.Pro2168Arg missense NM_001354898.2:c.6398C>G NP_001341827.1:p.Pro2133Arg missense NM_001354899.2:c.6389C>G NP_001341828.1:p.Pro2130Arg missense NM_001354900.2:c.6350C>G NP_001341829.1:p.Pro2117Arg missense NM_001354901.2:c.6296C>G NP_001341830.1:p.Pro2099Arg missense NM_001354902.2:c.6200C>G NP_001341831.1:p.Pro2067Arg missense NM_001354903.2:c.6170C>G NP_001341832.1:p.Pro2057Arg missense NM_001354904.2:c.6095C>G NP_001341833.1:p.Pro2032Arg missense NM_001354905.2:c.5993C>G NP_001341834.1:p.Pro1998Arg missense NM_001354906.2:c.5624C>G NP_001341835.1:p.Pro1875Arg missense NC_000005.10:g.112842067C>G NC_000005.9:g.112177764C>G NG_008481.4:g.154547C>G LRG_130:g.154547C>G LRG_130t1:c.6473C>G - Protein change
- P2158R, P2140R, P2057R, P2117R, P2133R, P1998R, P2032R, P2067R, P2099R, P2176R, P1875R, P2130R, P2168R
- Other names
-
p.P2158R:CCC>CGC
- Canonical SPDI
- NC_000005.10:112842066:C:G
-
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.
-
Exome Aggregation Consortium (ExAC) 0.00005
The Genome Aggregation Database (gnomAD), exomes 0.00005
The Genome Aggregation Database (gnomAD) 0.00007
Trans-Omics for Precision Medicine (TOPMed) 0.00010
- Links
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 |
- | - | |
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. |
|---|---|---|---|---|
| Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
|
Dec 21, 2022 | RCV000115112.26 | |
| Conflicting interpretations of pathogenicity (4) |
criteria provided, conflicting classifications
|
Feb 1, 2024 | RCV000122792.28 | |
| Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
|
Jan 7, 2019 | RCV000235096.14 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Sep 29, 2022 | RCV000587692.14 | |
|
APC-related disorder
|
Uncertain significance (1) |
no assertion criteria provided
|
Mar 20, 2024 | RCV003398710.5 |
| Uncertain significance (1) |
criteria provided, single submitter
|
Feb 5, 2024 | RCV003997227.2 |
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 07, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000694095.2
First in ClinVar: Mar 17, 2018 Last updated: Nov 08, 2019 |
Comment:
Variant summary: The variant, APC c.6473C>G (p.Pro2158Arg) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict … (more)
Variant summary: The variant, APC c.6473C>G (p.Pro2158Arg) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 5e-05 in 278626 control chromosomes (gnomAD and Azzopardi_2008). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. The variant, c.6473C>G has been reported in the literature in individuals affected with colorectal cancer, familial adenomatous polyposis, and breast cancer (Azzopardi_2008, Pearlman_2016, Zhang_2015). However, 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. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. (less)
|
|
|
Likely benign
(Mar 09, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000186636.9
First in ClinVar: Aug 06, 2014 Last updated: May 01, 2024 |
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more)
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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)
|
|
|
Uncertain significance
(Jun 23, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000538304.1
First in ClinVar: Jul 29, 2016 Last updated: Jul 29, 2016 |
Comment:
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or … (more)
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Reported in 1 proband; Clinvar: 4 vus (less)
Method: Genome/Exome Filtration
|
|
|
Uncertain significance
(Aug 01, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
GeneKor MSA
Accession: SCV000821820.1
First in ClinVar: Oct 10, 2018 Last updated: Oct 10, 2018 |
|
|
|
Uncertain significance
(May 28, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Familial adenomatous polyposis 1
Affected status: unknown
Allele origin:
unknown
|
Mendelics
Accession: SCV001136931.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
|
|
|
Uncertain significance
(Aug 03, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Familial adenomatous polyposis 1
Affected status: unknown
Allele origin:
germline
|
St. Jude Molecular Pathology, St. Jude Children's Research Hospital
Accession: SCV001775530.1
First in ClinVar: Aug 13, 2021 Last updated: Aug 13, 2021 |
|
|
|
Uncertain significance
(Dec 21, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000681800.6
First in ClinVar: Feb 19, 2018 Last updated: Feb 14, 2024 |
Comment:
This missense variant replaces proline with arginine at codon 2158 of the APC protein. Computational prediction is inconclusive regarding the impact of this variant on … (more)
This missense variant replaces proline with arginine at codon 2158 of the APC protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been observed in individuals affected with colorectal adenomas (PMID: 18199528), colorectal cancer (PMID: 27978560), breast cancer (PMID: 25186627) or referred for hereditary cancer screening (PMID: 31159747). This variant has also been identified in 14/281472 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)
|
|
|
Likely benign
(Feb 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Familial adenomatous polyposis 1
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000166049.13
First in ClinVar: Jun 15, 2014 Last updated: Feb 20, 2024 |
|
|
|
Uncertain significance
(Sep 29, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000149021.18
First in ClinVar: May 17, 2014 Last updated: Mar 04, 2023 |
Comment:
In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 21859464, 18199528, 27978560, … (more)
In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 21859464, 18199528, 27978560, 29148535, 25186627, 26580448, 29684080, 31159747) (less)
|
|
|
Uncertain Significance
(Feb 05, 2024)
|
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: SCV004840353.1
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 proline with arginine at codon 2158 of the APC protein. Computational prediction is inconclusive regarding the impact of this variant on … (more)
This missense variant replaces proline with arginine at codon 2158 of the APC protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been observed in individuals affected with colorectal adenomas (PMID: 18199528), colorectal cancer (PMID: 27978560), breast cancer (PMID: 25186627) or referred for hereditary cancer screening (PMID: 31159747). This variant has also been identified in 14/281472 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: 14
Zygosity: Single Heterozygote
|
|
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Uncertain significance
(Jul 24, 2014)
|
no assertion criteria provided
Method: clinical testing
|
Adenomatous polyposis coli
Affected status: unknown
Allele origin:
germline
|
Pathway Genomics
Accession: SCV000189871.1
First in ClinVar: Oct 19, 2014 Last updated: Oct 19, 2014 |
|
|
|
Uncertain significance
(Mar 20, 2024)
|
no assertion criteria provided
Method: clinical testing
|
APC-related condition
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV004111318.2
First in ClinVar: Nov 20, 2023 Last updated: Oct 08, 2024 |
Comment:
The APC c.6473C>G variant is predicted to result in the amino acid substitution p.Pro2158Arg. This variant has been reported in individuals with colorectal adenomas, at … (more)
The APC c.6473C>G variant is predicted to result in the amino acid substitution p.Pro2158Arg. This variant has been reported in individuals with colorectal adenomas, at least one colon cancer patient with mismatch repair-proficient tumor status (Azzopardi et al. 2008. PubMed ID: 18199528; Pearlman et al. 2017, eTable 2. PubMed ID: 27978560), and patients with a suspected hereditary cancer syndrome (Table S4, Bhai et al. 2021. PubMed ID: 34326862). This variant is reported in 0.012% of alleles in individuals of African descent in gnomAD and is classified as uncertain and likely benign in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/127313/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. (less)
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Comment:
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.
Comment:
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Reported in 1 proband; Clinvar: 4 vus
Comment:
This missense variant replaces proline with arginine at codon 2158 of the APC protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been observed in individuals affected with colorectal adenomas (PMID: 18199528), colorectal cancer (PMID: 27978560), breast cancer (PMID: 25186627) or referred for hereditary cancer screening (PMID: 31159747). This variant has also been identified in 14/281472 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.
Comment:
In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 21859464, 18199528, 27978560, 29148535, 25186627, 26580448, 29684080, 31159747)
Comment:
This missense variant replaces proline with arginine at codon 2158 of the APC protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been observed in individuals affected with colorectal adenomas (PMID: 18199528), colorectal cancer (PMID: 27978560), breast cancer (PMID: 25186627) or referred for hereditary cancer screening (PMID: 31159747). This variant has also been identified in 14/281472 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.
Comment:
The APC c.6473C>G variant is predicted to result in the amino acid substitution p.Pro2158Arg. This variant has been reported in individuals with colorectal adenomas, at least one colon cancer patient with mismatch repair-proficient tumor status (Azzopardi et al. 2008. PubMed ID: 18199528; Pearlman et al. 2017, eTable 2. PubMed ID: 27978560), and patients with a suspected hereditary cancer syndrome (Table S4, Bhai et al. 2021. PubMed ID: 34326862). This variant is reported in 0.012% of alleles in individuals of African descent in gnomAD and is classified as uncertain and likely benign in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/127313/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
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. |
Comment:
Variant summary: The variant, APC c.6473C>G (p.Pro2158Arg) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 5e-05 in 278626 control chromosomes (gnomAD and Azzopardi_2008). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. The variant, c.6473C>G has been reported in the literature in individuals affected with colorectal cancer, familial adenomatous polyposis, and breast cancer (Azzopardi_2008, Pearlman_2016, Zhang_2015). However, 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. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.
Comment:
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Reported in 1 proband; Clinvar: 4 vus
Comment:
This missense variant replaces proline with arginine at codon 2158 of the APC protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been observed in individuals affected with colorectal adenomas (PMID: 18199528), colorectal cancer (PMID: 27978560), breast cancer (PMID: 25186627) or referred for hereditary cancer screening (PMID: 31159747). This variant has also been identified in 14/281472 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.
Comment:
In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 21859464, 18199528, 27978560, 29148535, 25186627, 26580448, 29684080, 31159747)
Comment:
This missense variant replaces proline with arginine at codon 2158 of the APC protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been observed in individuals affected with colorectal adenomas (PMID: 18199528), colorectal cancer (PMID: 27978560), breast cancer (PMID: 25186627) or referred for hereditary cancer screening (PMID: 31159747). This variant has also been identified in 14/281472 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.
Comment:
The APC c.6473C>G variant is predicted to result in the amino acid substitution p.Pro2158Arg. This variant has been reported in individuals with colorectal adenomas, at least one colon cancer patient with mismatch repair-proficient tumor status (Azzopardi et al. 2008. PubMed ID: 18199528; Pearlman et al. 2017, eTable 2. PubMed ID: 27978560), and patients with a suspected hereditary cancer syndrome (Table S4, Bhai et al. 2021. PubMed ID: 34326862). This variant is reported in 0.012% of alleles in individuals of African descent in gnomAD and is classified as uncertain and likely benign in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/127313/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Analysis of hereditary cancer syndromes by using a panel of genes: novel and multiple pathogenic mutations. | Tsaousis GN | BMC cancer | 2019 | PMID: 31159747 |
| Unexpected cancer-predisposition gene variants in Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome patients without underlying germline PTEN mutations. | Yehia L | PLoS genetics | 2018 | PMID: 29684080 |
| Prevalence and Spectrum of Germline Cancer Susceptibility Gene Mutations Among Patients With Early-Onset Colorectal Cancer. | Pearlman R | JAMA oncology | 2017 | PMID: 27978560 |
| Germline Mutations in Predisposition Genes in Pediatric Cancer. | Zhang J | The New England journal of medicine | 2015 | PMID: 26580448 |
| Frequency of mutations in individuals with breast cancer referred for BRCA1 and BRCA2 testing using next-generation sequencing with a 25-gene panel. | Tung N | Cancer | 2015 | PMID: 25186627 |
| Messing up disorder: how do missense mutations in the tumor suppressor protein APC lead to cancer? | Minde DP | Molecular cancer | 2011 | PMID: 21859464 |
| Multiple rare nonsynonymous variants in the adenomatous polyposis coli gene predispose to colorectal adenomas. | Azzopardi D | Cancer research | 2008 | PMID: 18199528 |
Text-mined citations for rs587779804 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Nov 25, 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.