The c.164_165dupTT pathogenic mutation, located in coding exon 2 of the APC gene, results from a duplication of TT at nucleotide position 164, causing a translational frameshift with a predicted alternate stop codon (p.E56Lfs*15). Premature termination codons are typically deleterious in nature. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). As such, this alteration is classified as a disease-causing mutation. However, alterations that result in premature termination in coding exon 2 are associated with an attenuated phenotype and may have reduced penetrance compared to classic familial adenomatous polyposis syndrome. Clinical correlation is advised.
ClinVar Genomic variation as it relates to human health
NM_000038.6(APC):c.164_165dup (p.Glu56fs)
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.
(1)
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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
1
criteria provided, single submitter
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.164_165dup (p.Glu56fs)
Variation ID: 3412030 Accession: VCV003412030.1
- Type and length
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Duplication, 2 bp
- Location
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5: 112766353-112766354 (GRCh38) [ NCBI UCSC ] 5: 112102050-112102051 (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 13, 2025 Jan 13, 2025 Nov 15, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000038.6:c.164_165dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000029.2:p.Glu56fs frameshift NM_001127510.3:c.164_165dup NP_001120982.1:p.Glu56fs frameshift NM_001127511.3:c.194_195dup NP_001120983.2:p.Glu66fs frameshift NM_001354895.2:c.164_165dup NP_001341824.1:p.Glu56fs frameshift NM_001354896.2:c.164_165dup NP_001341825.1:p.Glu56fs frameshift NM_001354897.2:c.194_195dup NP_001341826.1:p.Glu66fs frameshift NM_001354898.2:c.89_90dup NP_001341827.1:p.Glu31fs frameshift NM_001354899.2:c.164_165dup NP_001341828.1:p.Glu56fs frameshift NM_001354900.2:c.-14_-13dup 5 prime UTR NM_001354901.2:c.-14_-13dup 5 prime UTR NM_001354902.2:c.194_195dup NP_001341831.1:p.Glu66fs frameshift NM_001354903.2:c.164_165dup NP_001341832.1:p.Glu56fs frameshift NM_001354904.2:c.89_90dup NP_001341833.1:p.Glu31fs frameshift NM_001354905.2:c.-14_-13dup 5 prime UTR NM_001354906.2:c.-872_-871dup 5 prime UTR NM_001407446.1:c.194_195dup NP_001394375.1:p.Glu66fs frameshift NM_001407447.1:c.164_165dup NP_001394376.1:p.Glu56fs frameshift NM_001407448.1:c.164_165dup NP_001394377.1:p.Glu56fs frameshift NM_001407449.1:c.164_165dup NP_001394378.1:p.Glu56fs frameshift NM_001407450.1:c.164_165dup NP_001394379.1:p.Glu56fs frameshift NM_001407451.1:c.89_90dup NP_001394380.1:p.Glu31fs frameshift NM_001407452.1:c.164_165dup NP_001394381.1:p.Glu56fs frameshift NM_001407453.1:c.-14_-13dup 5 prime UTR NM_001407454.1:c.164_165dup NP_001394383.1:p.Glu56fs frameshift NM_001407455.1:c.164_165dup NP_001394384.1:p.Glu56fs frameshift NM_001407456.1:c.164_165dup NP_001394385.1:p.Glu56fs frameshift NM_001407457.1:c.164_165dup NP_001394386.1:p.Glu56fs frameshift NM_001407458.1:c.164_165dup NP_001394387.1:p.Glu56fs frameshift NM_001407459.1:c.164_165dup NP_001394388.1:p.Glu56fs frameshift NM_001407460.1:c.164_165dup NP_001394389.1:p.Glu56fs frameshift NM_001407467.1:c.164_165dup NP_001394396.1:p.Glu56fs frameshift NM_001407469.1:c.164_165dup NP_001394398.1:p.Glu56fs frameshift NM_001407470.1:c.-872_-871dup 5 prime UTR NM_001407471.1:c.-872_-871dup 5 prime UTR NM_001407472.1:c.-872_-871dup 5 prime UTR NR_176365.1:n.334_335dup non-coding transcript variant NR_176366.1:n.567_568dup non-coding transcript variant NC_000005.10:g.112766354_112766355dup NC_000005.9:g.112102051_112102052dup NG_008481.4:g.78834_78835dup LRG_130:g.78834_78835dup LRG_130t1:c.164_165dup LRG_130p1:p.Glu56Leufs LRG_130t2:c.164_165dup LRG_130p2:p.Glu56Leufs LRG_130t3:c.164_165dup LRG_130p3:p.Glu56Leufs - Protein change
- E56fs, E31fs, E66fs
- Other names
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- Canonical SPDI
- NC_000005.10:112766353:TT:TTTT
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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 |
15241 | 15379 | |
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 15, 2024 | RCV004945525.1 |
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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Pathogenic
(Nov 15, 2024)
|
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: SCV005467735.1
First in ClinVar: Jan 13, 2025 Last updated: Jan 13, 2025 |
Comment:
The c.164_165dupTT pathogenic mutation, located in coding exon 2 of the APC gene, results from a duplication of TT at nucleotide position 164, causing a … (more)
The c.164_165dupTT pathogenic mutation, located in coding exon 2 of the APC gene, results from a duplication of TT at nucleotide position 164, causing a translational frameshift with a predicted alternate stop codon (p.E56Lfs*15). Premature termination codons are typically deleterious in nature. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). As such, this alteration is classified as a disease-causing mutation. However, alterations that result in premature termination in coding exon 2 are associated with an attenuated phenotype and may have reduced penetrance compared to classic familial adenomatous polyposis syndrome. Clinical correlation is advised. (less)
|
Comment:
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:
The c.164_165dupTT pathogenic mutation, located in coding exon 2 of the APC gene, results from a duplication of TT at nucleotide position 164, causing a translational frameshift with a predicted alternate stop codon (p.E56Lfs*15). Premature termination codons are typically deleterious in nature. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). As such, this alteration is classified as a disease-causing mutation. However, alterations that result in premature termination in coding exon 2 are associated with an attenuated phenotype and may have reduced penetrance compared to classic familial adenomatous polyposis syndrome. Clinical correlation is advised.
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 Jan 13, 2025
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.