ClinVar Genomic variation as it relates to human health
NM_000038.6(APC):c.7798_7801del (p.Gln2600fs)
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
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NM_000038.6(APC):c.7798_7801del (p.Gln2600fs)
Variation ID: 827255 Accession: VCV000827255.17
- Type and length
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Microsatellite, 4 bp
- Location
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Cytogenetic: 5q22.2 5: 112843388-112843391 (GRCh38) [ NCBI UCSC ] 5: 112179085-112179088 (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 Mar 16, 2020 Aug 11, 2024 May 27, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000038.6:c.7798_7801del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000029.2:p.Gln2600fs frameshift NM_000038.5:c.7798_7801delCAAA NM_001127510.3:c.7798_7801del NP_001120982.1:p.Gln2600fs frameshift NM_001127511.3:c.7744_7747del NP_001120983.2:p.Gln2582fs frameshift NM_001354895.2:c.7798_7801del NP_001341824.1:p.Gln2600fs frameshift NM_001354896.2:c.7852_7855del NP_001341825.1:p.Gln2618fs frameshift NM_001354897.2:c.7828_7831del NP_001341826.1:p.Gln2610fs frameshift NM_001354898.2:c.7723_7726del NP_001341827.1:p.Gln2575fs frameshift NM_001354899.2:c.7714_7717del NP_001341828.1:p.Gln2572fs frameshift NM_001354900.2:c.7675_7678del NP_001341829.1:p.Gln2559fs frameshift NM_001354901.2:c.7621_7624del NP_001341830.1:p.Gln2541fs frameshift NM_001354902.2:c.7525_7528del NP_001341831.1:p.Gln2509fs frameshift NM_001354903.2:c.7495_7498del NP_001341832.1:p.Gln2499fs frameshift NM_001354904.2:c.7420_7423del NP_001341833.1:p.Gln2474fs frameshift NM_001354905.2:c.7318_7321del NP_001341834.1:p.Gln2440fs frameshift NM_001354906.2:c.6949_6952del NP_001341835.1:p.Gln2317fs frameshift NC_000005.10:g.112843388CAAA[1] NC_000005.9:g.112179085CAAA[1] NG_008481.4:g.155868CAAA[1] LRG_130:g.155868CAAA[1] - Protein change
- Q2499fs, Q2559fs, Q2575fs, Q2610fs, Q2618fs, Q2317fs, Q2440fs, Q2541fs, Q2572fs, Q2582fs, Q2600fs, Q2474fs, Q2509fs
- Other names
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- Canonical SPDI
- NC_000005.10:112843387:CAAACAAA:CAAA
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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 | ||
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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 |
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. |
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Pathogenic (1) |
criteria provided, single submitter
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May 27, 2024 | RCV001026814.12 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 21, 2021 | RCV001776090.10 | |
Pathogenic/Likely pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Jul 3, 2023 | RCV002552418.12 |
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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Pathogenic
(Jan 21, 2021)
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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: SCV002013899.2
First in ClinVar: Nov 12, 2021 Last updated: Mar 04, 2023 |
Comment:
Frameshift variant predicted to result in protein truncation in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant … (more)
Frameshift variant predicted to result in protein truncation in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek 2016); Has not been previously published as pathogenic or benign to our knowledge (less)
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Pathogenic
(May 16, 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: SCV004043647.2
First in ClinVar: Oct 21, 2023 Last updated: Oct 28, 2023 |
Comment:
This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
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Likely pathogenic
(Feb 02, 2022)
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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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Baylor Genetics
Accession: SCV004207995.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Jul 03, 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:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001591769.4
First in ClinVar: May 10, 2021 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. A different truncation (p.Tyr2645Lysfs*14) that lies downstream of this variant has been determined to be … (more)
For these reasons, this variant has been classified as Pathogenic. 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. 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. ClinVar contains an entry for this variant (Variation ID: 827255). This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Gln2600Valfs*15) in the APC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 244 amino acid(s) of the APC protein. (less)
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Pathogenic
(May 27, 2024)
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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: SCV001189270.5
First in ClinVar: Mar 16, 2020 Last updated: Aug 11, 2024 |
Comment:
The c.7798_7801delCAAA pathogenic mutation, located in coding exon 15 of the APC gene, results from a deletion of 4 nucleotides at nucleotide positions 7798 to … (more)
The c.7798_7801delCAAA pathogenic mutation, located in coding exon 15 of the APC gene, results from a deletion of 4 nucleotides at nucleotide positions 7798 to 7801, causing a translational frameshift with a predicted alternate stop codon (p.Q2600Vfs*15). This alteration is expected to result in loss of function by premature protein truncation. As such, this alteration is interpreted as a disease-causing mutation. (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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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 |
Text-mined citations for rs1561618361 ...
HelpRecord last updated Nov 03, 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.