This sequence change creates a premature translational stop signal (p.Glu853*) in the APC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1991 amino acid(s) of the APC protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is expected to disrupt the EB1 and HDLG binding sites, which mediate interactions with the cytoskeleton (PMID: 15311282, 17293347). While functional studies have not been performed to directly test the effect on APC protein function, this suggests that disruption of the C-terminal portion of the protein is functionally important. A different truncation (p.Tyr2645Lysfs*14) that lies downstream of this variant has been determined to be pathogenic (PMID: 9824584, 1316610, 27081525, 8381579, 22135120, Invitae). This suggests that deletion of this region of the APC protein is causative of disease. For these reasons, this variant has been classified as Pathogenic.
ClinVar Genomic variation as it relates to human health
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- Interpretation:
-
Pathogenic
- Review status:
- criteria provided, single submitter
- Submissions:
- 1
- First in ClinVar:
- May 10, 2021
- Most recent Submission:
- Feb 7, 2023
- Last evaluated:
- Aug 24, 2021
- Accession:
- VCV001071632.7
- Variation ID:
- 1071632
- Description:
- single nucleotide variant
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NM_000038.6(APC):c.2557G>T (p.Glu853Ter)
- Allele ID
- 1060134
- Variant type
- single nucleotide variant
- Variant length
- 1 bp
- Cytogenetic location
- 5q22.2
- Genomic location
- 5: 112838151 (GRCh38) GRCh38 UCSC
- 5: 112173848 (GRCh37) GRCh37 UCSC
- HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000038.6:c.2557G>T MANE Select NP_000029.2:p.Glu853Ter nonsense NM_001127510.3:c.2557G>T NP_001120982.1:p.Glu853Ter nonsense NM_001127511.3:c.2503G>T NP_001120983.2:p.Glu835Ter nonsense NM_001354895.2:c.2557G>T NP_001341824.1:p.Glu853Ter nonsense NM_001354896.2:c.2611G>T NP_001341825.1:p.Glu871Ter nonsense NM_001354897.2:c.2587G>T NP_001341826.1:p.Glu863Ter nonsense NM_001354898.2:c.2482G>T NP_001341827.1:p.Glu828Ter nonsense NM_001354899.2:c.2473G>T NP_001341828.1:p.Glu825Ter nonsense NM_001354900.2:c.2434G>T NP_001341829.1:p.Glu812Ter nonsense NM_001354901.2:c.2380G>T NP_001341830.1:p.Glu794Ter nonsense NM_001354902.2:c.2284G>T NP_001341831.1:p.Glu762Ter nonsense NM_001354903.2:c.2254G>T NP_001341832.1:p.Glu752Ter nonsense NM_001354904.2:c.2179G>T NP_001341833.1:p.Glu727Ter nonsense NM_001354905.2:c.2077G>T NP_001341834.1:p.Glu693Ter nonsense NM_001354906.2:c.1708G>T NP_001341835.1:p.Glu570Ter nonsense NC_000005.10:g.112838151G>T NC_000005.9:g.112173848G>T NG_008481.4:g.150631G>T LRG_130:g.150631G>T - Protein change
- E570*, E693*, E727*, E752*, E762*, E794*, E812*, E825*, E828*, E835*, E853*, E863*, E871*
- Other names
- -
- Canonical SPDI
- NC_000005.10:112838150:G:T
- Functional consequence
- -
- Global minor allele frequency (GMAF)
- -
- Allele frequency
- -
- Links
- VarSome
Help
Aggregate interpretations per condition
| Interpreted condition | Interpretation | Number of submissions | Review status | Last evaluated | Variation/condition record |
|---|---|---|---|---|---|
| Pathogenic | 1 | criteria provided, single submitter | Aug 24, 2021 | RCV002551537.1 |
Help
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation | Variation viewer | Related variants | ||
|---|---|---|---|---|---|---|
| HI score Help | TS score Help | Within gene | All | |||
| APC | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
12277 | 12317 | |
Submitted interpretations and evidence
Help| Interpretation (Last evaluated) |
Review status (Assertion criteria) |
Condition (Inheritance) |
Submitter | More information | |
|---|---|---|---|---|---|
|
Pathogenic
(Aug 24, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Familial adenomatous polyposis 1
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV001583531.3
First in ClinVar: May 10, 2021 Last updated: Feb 07, 2023 |
Comment:
This sequence change creates a premature translational stop signal (p.Glu853*) in the APC gene. While this is not anticipated to result in nonsense mediated decay, … (more)
This sequence change creates a premature translational stop signal (p.Glu853*) in the APC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1991 amino acid(s) of the APC protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is expected to disrupt the EB1 and HDLG binding sites, which mediate interactions with the cytoskeleton (PMID: 15311282, 17293347). While functional studies have not been performed to directly test the effect on APC protein function, this suggests that disruption of the C-terminal portion of the protein is functionally important. A different truncation (p.Tyr2645Lysfs*14) that lies downstream of this variant has been determined to be pathogenic (PMID: 9824584, 1316610, 27081525, 8381579, 22135120, Invitae). This suggests that deletion of this region of the APC protein is causative of disease. For these reasons, this variant has been classified as Pathogenic. (less)
|
Functional evidence
Help| 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 this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Attenuated familial adenomatous polyposis with desmoids caused by an APC mutation. | Ikenoue T | Human genome variation | 2015 | PMID: 27081525 |
| Prevalence of skin lesions in familial adenomatous polyposis: a marker for presymptomatic diagnosis? | Burger B | The oncologist | 2011 | PMID: 22135120 |
| Regulated binding of adenomatous polyposis coli protein to actin. | Moseley JB | The Journal of biological chemistry | 2007 | PMID: 17293347 |
| EB1 and APC bind to mDia to stabilize microtubules downstream of Rho and promote cell migration. | Wen Y | Nature cell biology | 2004 | PMID: 15311282 |
| Variable phenotype of familial adenomatous polyposis in pedigrees with 3' mutation in the APC gene. | Brensinger JD | Gut | 1998 | PMID: 9824584 |
| Mutational analysis of patients with adenomatous polyposis: identical inactivating mutations in unrelated individuals. | Groden J | American journal of human genetics | 1993 | PMID: 8381579 |
| Germ-line mutations of the APC gene in 53 familial adenomatous polyposis patients. | Miyoshi Y | Proceedings of the National Academy of Sciences of the United States of America | 1992 | PMID: 1316610 |
Record last updated Jun 04, 2023