ClinVar Genomic variation as it relates to human health
NM_000038.6(APC):c.233_236del (p.Asp78fs)
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.233_236del (p.Asp78fs)
Variation ID: 418005 Accession: VCV000418005.21
- Type and length
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Deletion, 4 bp
- Location
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Cytogenetic: 5q22.2 5: 112767198-112767201 (GRCh38) [ NCBI UCSC ] 5: 112102895-112102898 (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 Apr 15, 2024 Jan 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000038.6:c.233_236del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000029.2:p.Asp78fs frameshift NM_000038.5:c.233_236del NM_001127510.3:c.233_236del NP_001120982.1:p.Asp78fs frameshift NM_001127511.3:c.263_266del NP_001120983.2:p.Asp88fs frameshift NM_001354895.2:c.233_236del NP_001341824.1:p.Asp78fs frameshift NM_001354896.2:c.233_236del NP_001341825.1:p.Asp78fs frameshift NM_001354897.2:c.263_266del NP_001341826.1:p.Asp88fs frameshift NM_001354898.2:c.158_161del NP_001341827.1:p.Asp53fs frameshift NM_001354899.2:c.233_236del NP_001341828.1:p.Asp78fs frameshift NM_001354900.2:c.56_59del NP_001341829.1:p.Asp19fs frameshift NM_001354901.2:c.56_59del NP_001341830.1:p.Asp19fs frameshift NM_001354902.2:c.263_266del NP_001341831.1:p.Asp88fs frameshift NM_001354903.2:c.233_236del NP_001341832.1:p.Asp78fs frameshift NM_001354904.2:c.158_161del NP_001341833.1:p.Asp53fs frameshift NM_001354905.2:c.56_59del NP_001341834.1:p.Asp19fs frameshift NM_001354906.2:c.-803_-800del 5 prime UTR NC_000005.10:g.112767201_112767204del NC_000005.9:g.112102898_112102901del NG_008481.4:g.79681_79684del LRG_130:g.79681_79684del - Protein change
- D53fs, D19fs, D78fs, D88fs
- Other names
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- Canonical SPDI
- NC_000005.10:112767197:TAGATAG:TAG
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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
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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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
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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 |
14000 | 14134 |
Conditions - Germline
Condition
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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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 (2) |
criteria provided, multiple submitters, no conflicts
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Jan 1, 2024 | RCV000481173.15 | |
Pathogenic (1) |
criteria provided, single submitter
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Dec 29, 2022 | RCV000492026.12 | |
Pathogenic (1) |
criteria provided, single submitter
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Oct 16, 2021 | RCV001778973.9 | |
Pathogenic (1) |
criteria provided, multiple submitters, no conflicts
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Apr 25, 2023 | RCV002525748.10 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 3, 2023 | RCV003743729.1 | |
Pathogenic (1) |
criteria provided, single submitter
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Nov 9, 2023 | RCV003962330.1 |
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
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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
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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
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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
(Oct 16, 2021)
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criteria provided, single submitter
Method: clinical testing
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Familial multiple polyposis syndrome
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV002014930.1
First in ClinVar: Nov 20, 2021 Last updated: Nov 20, 2021 |
Comment:
Variant summary: APC c.233_236delATAG (p.Asp78AlafsX7) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: APC c.233_236delATAG (p.Asp78AlafsX7) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251310 control chromosomes (gnomAD). c.233_236delATAG has been reported in the literature in individuals affected with attenuated form of Familial Adenomatous Polyposis (example, Spirio_1993, Wu_2001, Wang_2019). This variant is also known as c.232_235del4 and c.230_233_delTAGA in the literature (Spirio_1993, Wu_2001 and Wang_2019). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Jun 17, 2022)
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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: SCV000564557.6
First in ClinVar: Apr 27, 2017 Last updated: Mar 04, 2023 |
Comment:
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not … (more)
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Observed in individuals with a personal or family history consistent with pathogenic variants in this gene referred for genetic testing at GeneDx and in the published literature (Spirio 1993); This variant is associated with the following publications: (PMID: 8252630) (less)
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Pathogenic
(Dec 29, 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: SCV000579852.6
First in ClinVar: Jun 25, 2017 Last updated: Apr 15, 2023 |
Comment:
The c.233_236delATAG pathogenic mutation, located in coding exon 3 of the APC gene, results from a deletion of 4 nucleotides at nucleotide positions 233 to … (more)
The c.233_236delATAG pathogenic mutation, located in coding exon 3 of the APC gene, results from a deletion of 4 nucleotides at nucleotide positions 233 to 236, causing a translational frameshift with a predicted alternate stop codon (p.D78Afs*7). This mutation was identified in a kindred affected with attenuated FAP (Spirio L et al. Cell, 1993 Dec;75:951-7). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (less)
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Pathogenic
(Apr 25, 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: SCV004043957.2
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
(Jan 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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Invitae
Accession: SCV000647230.8
First in ClinVar: Dec 26, 2017 Last updated: Feb 20, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 418005). This variant is also known … (more)
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 418005). This variant is also known as c.232_235del4. This premature translational stop signal has been observed in individual(s) with attenuated familial adenomatous polyposis (AFAP) (PMID: 8252630). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Asp78Alafs*7) 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). (less)
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Pathogenic
(Nov 09, 2023)
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criteria provided, single submitter
Method: clinical testing
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APC-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004782717.1
First in ClinVar: Mar 16, 2024 Last updated: Mar 16, 2024 |
Comment:
The APC c.233_236delATAG variant is predicted to result in a frameshift and premature protein termination (p.Asp78Alafs*7). This variant has been reported in a family to … (more)
The APC c.233_236delATAG variant is predicted to result in a frameshift and premature protein termination (p.Asp78Alafs*7). This variant has been reported in a family to be causative for attenuated adenomatous polyposis coli (Spirio et al. 1993. PubMed ID: 8252630, kindred 6). This variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is interpreted as pathogenic in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/418005/?new_evidence=true). Frameshift variants in APC are expected to be pathogenic. This variant is interpreted as pathogenic. (less)
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Pathogenic
(Jan 01, 2024)
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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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CeGaT Center for Human Genetics Tuebingen
Accession: SCV004185292.3
First in ClinVar: Dec 24, 2023 Last updated: Apr 15, 2024 |
Comment:
APC: PP1:Strong, PVS1:Strong, PM2, PP4
Number of individuals with the variant: 2
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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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Adenomatous Polyposis Coli Gene Mutations in 22 Chinese Pedigrees with Familial Adenomatous Polyposis. | Wang D | Medical science monitor : international medical journal of experimental and clinical research | 2019 | PMID: 31113927 |
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 |
Detection of sequence variations in the adenomatous polyposis coli (APC) gene using denaturing high-performance liquid chromatography. | Wu G | Genetic testing | 2001 | PMID: 11960572 |
Alleles of the APC gene: an attenuated form of familial polyposis. | Spirio L | Cell | 1993 | PMID: 8252630 |
Linkage of a variant or attenuated form of adenomatous polyposis coli to the adenomatous polyposis coli (APC) locus. | Spirio L | American journal of human genetics | 1992 | PMID: 1319115 |
Text-mined citations for rs1064793020 ...
HelpRecord last updated Apr 15, 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.