Variant summary: APC c.3803dupC (p.Ile1269AsnfsX7) results in a premature termination codon, which is not predicted to undergo nonsense-mediated decay. Variants downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 250524 control chromosomes. To our knowledge, no occurrence of c.3803dupC in individuals affected with Familial Adenomatous Polyposis and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.
ClinVar Genomic variation as it relates to human health
NM_000038.6(APC):c.3803dup (p.Ile1269fs)
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.
Pathogenic
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.3803dup (p.Ile1269fs)
Variation ID: 2682626 Accession: VCV002682626.2
- Type and length
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Duplication, 1 bp
- Location
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Cytogenetic: 5q22.2 5: 112839395-112839396 (GRCh38) [ NCBI UCSC ] 5: 112175092-112175093 (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 Jan 6, 2024 Jul 23, 2024 Apr 1, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000038.6:c.3803dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000029.2:p.Ile1269fs frameshift NM_000038.6:c.3803dupC MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
frameshift NM_001127510.3:c.3803dup NP_001120982.1:p.Ile1269fs frameshift NM_001127511.3:c.3749dup NP_001120983.2:p.Ile1251fs frameshift NM_001354895.2:c.3803dup NP_001341824.1:p.Ile1269fs frameshift NM_001354896.2:c.3857dup NP_001341825.1:p.Ile1287fs frameshift NM_001354897.2:c.3833dup NP_001341826.1:p.Ile1279fs frameshift NM_001354898.2:c.3728dup NP_001341827.1:p.Ile1244fs frameshift NM_001354899.2:c.3719dup NP_001341828.1:p.Ile1241fs frameshift NM_001354900.2:c.3680dup NP_001341829.1:p.Ile1228fs frameshift NM_001354901.2:c.3626dup NP_001341830.1:p.Ile1210fs frameshift NM_001354902.2:c.3530dup NP_001341831.1:p.Ile1178fs frameshift NM_001354903.2:c.3500dup NP_001341832.1:p.Ile1168fs frameshift NM_001354904.2:c.3425dup NP_001341833.1:p.Ile1143fs frameshift NM_001354905.2:c.3323dup NP_001341834.1:p.Ile1109fs frameshift NM_001354906.2:c.2954dup NP_001341835.1:p.Ile986fs frameshift NM_001407446.1:c.3887dup NP_001394375.1:p.Ile1297fs frameshift NM_001407447.1:c.3857dup NP_001394376.1:p.Ile1287fs frameshift NM_001407448.1:c.3857dup NP_001394377.1:p.Ile1287fs frameshift NM_001407449.1:c.3857dup NP_001394378.1:p.Ile1287fs frameshift NM_001407450.1:c.3803dup NP_001394379.1:p.Ile1269fs frameshift NM_001407451.1:c.3782dup NP_001394380.1:p.Ile1262fs frameshift NM_001407452.1:c.3773dup NP_001394381.1:p.Ile1259fs frameshift NM_001407453.1:c.3626dup NP_001394382.1:p.Ile1210fs frameshift NM_001407454.1:c.3554dup NP_001394383.1:p.Ile1186fs frameshift NM_001407455.1:c.3554dup NP_001394384.1:p.Ile1186fs frameshift NM_001407456.1:c.3554dup NP_001394385.1:p.Ile1186fs frameshift NM_001407457.1:c.3554dup NP_001394386.1:p.Ile1186fs frameshift NM_001407458.1:c.3500dup NP_001394387.1:p.Ile1168fs frameshift NM_001407459.1:c.3500dup NP_001394388.1:p.Ile1168fs frameshift NM_001407460.1:c.3500dup NP_001394389.1:p.Ile1168fs frameshift NM_001407467.1:c.3416dup NP_001394396.1:p.Ile1140fs frameshift NM_001407469.1:c.3416dup NP_001394398.1:p.Ile1140fs frameshift NM_001407470.1:c.2954dup NP_001394399.1:p.Ile986fs frameshift NM_001407471.1:c.2651dup NP_001394400.1:p.Ile885fs frameshift NM_001407472.1:c.2651dup NP_001394401.1:p.Ile885fs frameshift NR_176365.1:n.3638dup non-coding transcript variant NR_176366.1:n.4057dup non-coding transcript variant NC_000005.10:g.112839397dup NC_000005.9:g.112175094dup NG_008481.4:g.151877dup LRG_130:g.151877dup LRG_130t1:c.3803dup LRG_130p1:p.Ile1269Asnfs LRG_130t2:c.3803dup LRG_130p2:p.Ile1269Asnfs LRG_130t3:c.3803dup LRG_130p3:p.Ile1269Asnfs - Protein change
- I1109fs, I1140fs, I1143fs, I1168fs, I1178fs, I1186fs, I1210fs, I1228fs, I1241fs, I1244fs, I1251fs, I1259fs, I1262fs, I1269fs, I1279fs, I1287fs, I1297fs, I885fs, I986fs
- Other names
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- Canonical SPDI
- NC_000005.10:112839395:CC:CCC
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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. |
|---|---|---|---|---|
| Pathogenic (1) |
criteria provided, single submitter
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Nov 20, 2023 | RCV003479999.1 | |
| Pathogenic (1) |
criteria provided, single submitter
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Apr 1, 2024 | RCV004593296.1 |
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
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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Pathogenic
(Nov 20, 2023)
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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: SCV004222885.1
First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 |
Comment:
Variant summary: APC c.3803dupC (p.Ile1269AsnfsX7) results in a premature termination codon, which is not predicted to undergo nonsense-mediated decay. Variants downstream of this position have … (more)
Variant summary: APC c.3803dupC (p.Ile1269AsnfsX7) results in a premature termination codon, which is not predicted to undergo nonsense-mediated decay. Variants downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 250524 control chromosomes. To our knowledge, no occurrence of c.3803dupC in individuals affected with Familial Adenomatous Polyposis and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
|
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Pathogenic
(Apr 01, 2024)
|
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: SCV005083591.1
First in ClinVar: Jul 23, 2024 Last updated: Jul 23, 2024 |
Comment:
This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
|
Comment:
Comment:
This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
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:
Variant summary: APC c.3803dupC (p.Ile1269AsnfsX7) results in a premature termination codon, which is not predicted to undergo nonsense-mediated decay. Variants downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 250524 control chromosomes. To our knowledge, no occurrence of c.3803dupC in individuals affected with Familial Adenomatous Polyposis and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.
Comment:
This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
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 Jul 23, 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.