This missense variant replaces isoleucine with valine at codon 2595 of the APC protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with APC-related disorders in the literature. This variant has not been identified 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.
ClinVar Genomic variation as it relates to human health
NM_000038.6(APC):c.7783A>G (p.Ile2595Val)
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.
(2)
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.
Uncertain significance
2
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000038.6(APC):c.7783A>G (p.Ile2595Val)
Variation ID: 1760611 Accession: VCV001760611.3
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 5q22.2 5: 112843377 (GRCh38) [ NCBI UCSC ] 5: 112179074 (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 Nov 29, 2022 May 1, 2024 Sep 4, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000038.6:c.7783A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000029.2:p.Ile2595Val missense NM_001127510.3:c.7783A>G NP_001120982.1:p.Ile2595Val missense NM_001127511.3:c.7729A>G NP_001120983.2:p.Ile2577Val missense NM_001354895.2:c.7783A>G NP_001341824.1:p.Ile2595Val missense NM_001354896.2:c.7837A>G NP_001341825.1:p.Ile2613Val missense NM_001354897.2:c.7813A>G NP_001341826.1:p.Ile2605Val missense NM_001354898.2:c.7708A>G NP_001341827.1:p.Ile2570Val missense NM_001354899.2:c.7699A>G NP_001341828.1:p.Ile2567Val missense NM_001354900.2:c.7660A>G NP_001341829.1:p.Ile2554Val missense NM_001354901.2:c.7606A>G NP_001341830.1:p.Ile2536Val missense NM_001354902.2:c.7510A>G NP_001341831.1:p.Ile2504Val missense NM_001354903.2:c.7480A>G NP_001341832.1:p.Ile2494Val missense NM_001354904.2:c.7405A>G NP_001341833.1:p.Ile2469Val missense NM_001354905.2:c.7303A>G NP_001341834.1:p.Ile2435Val missense NM_001354906.2:c.6934A>G NP_001341835.1:p.Ile2312Val missense NM_001407446.1:c.7867A>G NP_001394375.1:p.Ile2623Val missense NM_001407447.1:c.7837A>G NP_001394376.1:p.Ile2613Val missense NM_001407448.1:c.7837A>G NP_001394377.1:p.Ile2613Val missense NM_001407449.1:c.7837A>G NP_001394378.1:p.Ile2613Val missense NM_001407450.1:c.7783A>G NP_001394379.1:p.Ile2595Val missense NM_001407451.1:c.7762A>G NP_001394380.1:p.Ile2588Val missense NM_001407452.1:c.7753A>G NP_001394381.1:p.Ile2585Val missense NM_001407453.1:c.7606A>G NP_001394382.1:p.Ile2536Val missense NM_001407454.1:c.7534A>G NP_001394383.1:p.Ile2512Val missense NM_001407455.1:c.7534A>G NP_001394384.1:p.Ile2512Val missense NM_001407456.1:c.7534A>G NP_001394385.1:p.Ile2512Val missense NM_001407457.1:c.7534A>G NP_001394386.1:p.Ile2512Val missense NM_001407458.1:c.7480A>G NP_001394387.1:p.Ile2494Val missense NM_001407459.1:c.7480A>G NP_001394388.1:p.Ile2494Val missense NM_001407460.1:c.7480A>G NP_001394389.1:p.Ile2494Val missense NM_001407467.1:c.7396A>G NP_001394396.1:p.Ile2466Val missense NM_001407469.1:c.7396A>G NP_001394398.1:p.Ile2466Val missense NM_001407470.1:c.6934A>G NP_001394399.1:p.Ile2312Val missense NM_001407471.1:c.6631A>G NP_001394400.1:p.Ile2211Val missense NM_001407472.1:c.6631A>G NP_001394401.1:p.Ile2211Val missense NR_176365.1:n.7618A>G NR_176366.1:n.8037A>G NC_000005.10:g.112843377A>G NC_000005.9:g.112179074A>G NG_008481.4:g.155857A>G LRG_130:g.155857A>G LRG_130t1:c.7783A>G LRG_130p1:p.Ile2595Val LRG_130t2:c.7783A>G LRG_130p2:p.Ile2595Val LRG_130t3:c.7783A>G LRG_130p3:p.Ile2595Val - Protein change
- I2211V, I2605V, I2435V, I2494V, I2554V, I2585V, I2588V, I2623V, I2312V, I2504V, I2567V, I2577V, I2595V, I2613V, I2466V, I2469V, I2512V, I2536V, I2570V
- Other names
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- Canonical SPDI
- NC_000005.10:112843376: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.
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- 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. |
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| APC | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
14965 | 15103 | |
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 (1) |
criteria provided, single submitter
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Sep 25, 2022 | RCV002409830.2 | |
| Uncertain significance (1) |
criteria provided, single submitter
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Sep 4, 2023 | RCV004005756.2 |
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. |
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|---|---|---|---|---|---|
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Uncertain Significance
(Sep 04, 2023)
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criteria provided, single submitter
Method: clinical testing
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Classic or attenuated familial adenomatous polyposis
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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All of Us Research Program, National Institutes of Health
Accession: SCV004830419.1
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 isoleucine with valine at codon 2595 of the APC protein. Computational prediction suggests that this variant may not impact protein structure … (more)
This missense variant replaces isoleucine with valine at codon 2595 of the APC protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with APC-related disorders in the literature. This variant has not been identified 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: 1
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Uncertain significance
(Sep 25, 2022)
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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: SCV002674703.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The p.I2595V variant (also known as c.7783A>G), located in coding exon 15 of the APC gene, results from an A to G substitution at nucleotide … (more)
The p.I2595V variant (also known as c.7783A>G), located in coding exon 15 of the APC gene, results from an A to G substitution at nucleotide position 7783. The isoleucine at codon 2595 is replaced by valine, an amino acid with highly similar properties. This amino acid position is conserved. 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)
|
Comment:
Comment:
The p.I2595V variant (also known as c.7783A>G), located in coding exon 15 of the APC gene, results from an A to G substitution at nucleotide position 7783. The isoleucine at codon 2595 is replaced by valine, an amino acid with highly similar properties. This amino acid position is conserved. 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.
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:
This missense variant replaces isoleucine with valine at codon 2595 of the APC protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with APC-related disorders in the literature. This variant has not been identified 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 p.I2595V variant (also known as c.7783A>G), located in coding exon 15 of the APC gene, results from an A to G substitution at nucleotide position 7783. The isoleucine at codon 2595 is replaced by valine, an amino acid with highly similar properties. This amino acid position is conserved. 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.
Citations for germline classification of this variant
Help| There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for this variant ...
HelpRecord last updated May 08, 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.