This deletion of one nucleotide in APC is denoted c.298delG at the cDNA level and p.Glu100LysfsX25 (E100KfsX25) at the protein level. The normal sequence, with the base that is deleted in brackets, is CCGG[delG]AAGG. The deletion causes a frameshift which changes a Glutamic Acid to a Lysine at codon 100, and creates a premature stop codon at position 25 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. APC c.298delG has been identified in a patient with fundic gland polyposis and a family history of colon cancer and polyps (Ohtaka 2011). Based on the currently available information, we consider this deletion to be a likely pathogenic variant.
ClinVar Genomic variation as it relates to human health
NM_000038.6(APC):c.298del (p.Glu100fs)
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.
(6)
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.
Pathogenic/Likely pathogenic
6
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.298del (p.Glu100fs)
Variation ID: 419991 Accession: VCV000419991.13
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 5q22.2 5: 112767264 (GRCh38) [ NCBI UCSC ] 5: 112102961 (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 27, 2017 Feb 14, 2024 Oct 23, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000038.6:c.298del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000029.2:p.Glu100fs frameshift NM_001127510.3:c.298del NP_001120982.1:p.Glu100fs frameshift NM_001127511.3:c.328del NP_001120983.2:p.Glu110fs frameshift NM_001354895.2:c.298del NP_001341824.1:p.Glu100fs frameshift NM_001354896.2:c.298del NP_001341825.1:p.Glu100fs frameshift NM_001354897.2:c.328del NP_001341826.1:p.Glu110fs frameshift NM_001354898.2:c.223del NP_001341827.1:p.Glu75fs frameshift NM_001354899.2:c.298del NP_001341828.1:p.Glu100fs frameshift NM_001354900.2:c.121del NP_001341829.1:p.Glu41fs frameshift NM_001354901.2:c.121del NP_001341830.1:p.Glu41fs frameshift NM_001354902.2:c.328del NP_001341831.1:p.Glu110fs frameshift NM_001354903.2:c.298del NP_001341832.1:p.Glu100fs frameshift NM_001354904.2:c.223del NP_001341833.1:p.Glu75fs frameshift NM_001354905.2:c.121del NP_001341834.1:p.Glu41fs frameshift NM_001354906.2:c.-738del 5 prime UTR NC_000005.10:g.112767266del NC_000005.9:g.112102963del NG_008481.4:g.79746del LRG_130:g.79746del - Protein change
- E100fs, E75fs, E110fs, E41fs
- Other names
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- Canonical SPDI
- NC_000005.10:112767263:GGG:GG
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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. |
|||
| APC | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
14981 | 15119 | |
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. |
|---|---|---|---|---|
| Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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May 5, 2017 | RCV000486524.9 | |
| Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
|
Oct 23, 2023 | RCV002525821.14 |
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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Likely pathogenic
(Oct 03, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000568263.4
First in ClinVar: Apr 27, 2017 Last updated: Apr 27, 2017 |
Comment:
This deletion of one nucleotide in APC is denoted c.298delG at the cDNA level and p.Glu100LysfsX25 (E100KfsX25) at the protein level. The normal sequence, with … (more)
This deletion of one nucleotide in APC is denoted c.298delG at the cDNA level and p.Glu100LysfsX25 (E100KfsX25) at the protein level. The normal sequence, with the base that is deleted in brackets, is CCGG[delG]AAGG. The deletion causes a frameshift which changes a Glutamic Acid to a Lysine at codon 100, and creates a premature stop codon at position 25 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. APC c.298delG has been identified in a patient with fundic gland polyposis and a family history of colon cancer and polyps (Ohtaka 2011). Based on the currently available information, we consider this deletion to be a likely pathogenic variant. (less)
|
|
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Likely pathogenic
(May 05, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000600071.2
First in ClinVar: Apr 27, 2017 Last updated: Jan 01, 2022 |
|
|
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Pathogenic
(Apr 25, 2023)
|
criteria provided, single submitter
Method: clinical testing
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Familial adenomatous polyposis 1
Affected status: unknown
Allele origin:
unknown
|
Myriad Genetics, Inc.
Accession: SCV004044238.2
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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Pathogenic
(Aug 12, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Familial adenomatous polyposis 1
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004200441.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
|
|
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Pathogenic
(Oct 23, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Familial adenomatous polyposis 1
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000768278.4
First in ClinVar: May 28, 2018 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Glu100Lysfs*25) in the APC gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Glu100Lysfs*25) in the APC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in APC are known to be pathogenic (PMID: 17963004, 20685668). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with familial adenomatous polyposis (PMID: 21646762). ClinVar contains an entry for this variant (Variation ID: 419991). For these reasons, this variant has been classified as Pathogenic. (less)
|
|
|
not provided
(-)
|
no classification provided
Method: phenotyping only
|
Familial adenomatous polyposis 1
Affected status: yes
Allele origin:
unknown
|
GenomeConnect, ClinGen
Accession: SCV002075247.2
First in ClinVar: Feb 11, 2022 Last updated: Jan 07, 2023 |
Comment:
Variant classified as Likely pathogenic and reported on 10-03-2016 by Lab or GTR ID 507401. GenomeConnect assertions are reported exactly as they appear on the … (more)
Variant classified as Likely pathogenic and reported on 10-03-2016 by Lab or GTR ID 507401. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. (less)
Clinical Features:
Family history of cancer (present) , Adenomatous colonic polyposis (present)
Indication for testing: Diagnostic
Age: 30-39 years
Sex: female
Method: Gene Panel Sequencing
Testing laboratory: BioReference Health
Date variant was reported to submitter: 2016-10-03
Testing laboratory interpretation: Likely pathogenic
|
Comment:
Comment:
This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
Comment:
This sequence change creates a premature translational stop signal (p.Glu100Lysfs*25) in the APC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in APC are known to be pathogenic (PMID: 17963004, 20685668). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with familial adenomatous polyposis (PMID: 21646762). ClinVar contains an entry for this variant (Variation ID: 419991). For these reasons, this variant has been classified as Pathogenic.
Comment:
Variant classified as Likely pathogenic and reported on 10-03-2016 by Lab or GTR ID 507401. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
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 deletion of one nucleotide in APC is denoted c.298delG at the cDNA level and p.Glu100LysfsX25 (E100KfsX25) at the protein level. The normal sequence, with the base that is deleted in brackets, is CCGG[delG]AAGG. The deletion causes a frameshift which changes a Glutamic Acid to a Lysine at codon 100, and creates a premature stop codon at position 25 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. APC c.298delG has been identified in a patient with fundic gland polyposis and a family history of colon cancer and polyps (Ohtaka 2011). Based on the currently available information, we consider this deletion to be a likely pathogenic variant.
Comment:
This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
Comment:
This sequence change creates a premature translational stop signal (p.Glu100Lysfs*25) in the APC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in APC are known to be pathogenic (PMID: 17963004, 20685668). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with familial adenomatous polyposis (PMID: 21646762). ClinVar contains an entry for this variant (Variation ID: 419991). For these reasons, this variant has been classified as Pathogenic.
Comment:
Variant classified as Likely pathogenic and reported on 10-03-2016 by Lab or GTR ID 507401. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| [A family with attenuated familial adenomatous polyposis identified because of fundic gland polyposis]. | Ohtaka M | Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology | 2011 | PMID: 21646762 |
| Germline APC mutation spectrum derived from 863 genomic variations identified through a 15-year medical genetics service to French patients with FAP. | Lagarde A | Journal of medical genetics | 2010 | PMID: 20685668 |
| Mutational screening of the APC gene in Chilean families with familial adenomatous polyposis: nine novel truncating mutations. | De la Fuente MK | Diseases of the colon and rectum | 2007 | PMID: 17963004 |
Text-mined citations for rs1064794224 ...
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.