ClinVar Genomic variation as it relates to human health
NM_000038.6(APC):c.5582_5585del (p.Asp1860_Ser1861insTer)
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.5582_5585del (p.Asp1860_Ser1861insTer)
Variation ID: 821 Accession: VCV000000821.5
- Type and length
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Deletion, 4 bp
- Location
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Cytogenetic: 5q22.2 5: 112841174-112841177 (GRCh38) [ NCBI UCSC ] 5: 112176871-112176874 (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 4, 2013 Feb 14, 2024 Apr 17, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000038.6:c.5582_5585del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000029.2:p.Asp1860_Ser1861insTer nonsense NM_001127510.3:c.5582_5585del NP_001120982.1:p.Asp1860_Ser1861insTer nonsense NM_001127511.3:c.5528_5531del NP_001120983.2:p.Asp1842_Ser1843insTer nonsense NM_001354895.2:c.5582_5585del NP_001341824.1:p.Asp1860_Ser1861insTer nonsense NM_001354896.2:c.5636_5639del NP_001341825.1:p.Asp1878_Ser1879insTer nonsense NM_001354897.2:c.5612_5615del NP_001341826.1:p.Asp1870_Ser1871insTer nonsense NM_001354898.2:c.5507_5510del NP_001341827.1:p.Asp1835_Ser1836insTer nonsense NM_001354899.2:c.5498_5501del NP_001341828.1:p.Asp1832_Ser1833insTer nonsense NM_001354900.2:c.5459_5462del NP_001341829.1:p.Asp1819_Ser1820insTer nonsense NM_001354901.2:c.5405_5408del NP_001341830.1:p.Asp1801_Ser1802insTer nonsense NM_001354902.2:c.5309_5312del NP_001341831.1:p.Asp1769_Ser1770insTer nonsense NM_001354903.2:c.5279_5282del NP_001341832.1:p.Asp1759_Ser1760insTer nonsense NM_001354904.2:c.5204_5207del NP_001341833.1:p.Asp1734_Ser1735insTer nonsense NM_001354905.2:c.5102_5105del NP_001341834.1:p.Asp1700_Ser1701insTer nonsense NM_001354906.2:c.4733_4736del NP_001341835.1:p.Asp1577_Ser1578insTer nonsense NC_000005.10:g.112841176_112841179del NC_000005.9:g.112176873_112176876del NG_008481.4:g.153656_153659del LRG_130:g.153656_153659del - Protein change
- Other names
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- Canonical SPDI
- NC_000005.10:112841173:TTCTTT:TT
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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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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 |
14091 | 14225 |
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
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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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Feb 8, 2023 | RCV000000863.4 | |
Pathogenic (1) |
criteria provided, single submitter
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Dec 11, 2017 | RCV000779705.1 | |
Pathogenic (1) |
criteria provided, single submitter
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Apr 17, 2023 | RCV003534304.1 |
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
(Dec 11, 2017)
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criteria provided, single submitter
Method: clinical testing
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Familial adenomatous polyposis
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000916459.1
First in ClinVar: Jun 02, 2019 Last updated: Jun 02, 2019 |
Comment:
Variant summary: The APC c.5582_5585delCTTT (p.Ser1861fsX1) variant results in a termination codon in the last exon, however deletes a large number of amino acids (i.e. … (more)
Variant summary: The APC c.5582_5585delCTTT (p.Ser1861fsX1) variant results in a termination codon in the last exon, however deletes a large number of amino acids (i.e. deletes the last 981 amino acids). Truncations downstream of this position have been classified as pathogenic/likely pathogenic by clinical laboratories in ClinVar (e.g. c.5952_5955delTG, c.5973delG, c.6053delC, etc.). This variant is absent in 245758 control chromosomes (gnomAD). This variant has been reported in a large Dutch family with attenuated familial adenomatous polyposis where it co-segregated with disease (van der Luijt_1996). Western blot analysis of lymphoblastoid cell lines derived from affected family members from this kindred showed only the wild-type APC protein, showing that it does not result into stable truncated APC protein. Multiple reputable databases have classified this variant as pathogenic. Taken together, this variant is classified as pathogenic. (less)
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Pathogenic
(Feb 08, 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: SCV004018758.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023 |
Comment:
This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.
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Pathogenic
(Apr 17, 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: SCV003439279.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the APC protein in which other variant(s) (p.Tyr2645Lysfs*14) have … (more)
For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the APC protein in which other variant(s) (p.Tyr2645Lysfs*14) have been determined to be pathogenic (PMID: 1316610, 8381579, 9824584, 22135120, 27081525; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 821). This variant is also known as 1860delTTCT. This premature translational stop signal has been observed in individual(s) with attenuated familial adenomatous polyposis (PMID: 8931709, 17489848). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser1861*) in the APC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 983 amino acid(s) of the APC protein. (less)
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Pathogenic
(Dec 01, 1996)
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no assertion criteria provided
Method: literature only
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FAMILIAL ADENOMATOUS POLYPOSIS 1, ATTENUATED
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000021013.1
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
Comment on evidence:
In a large Dutch family with attenuated FAP1 (see 175100), van der Luijt et al. (1996) identified a 4-bp (TTCT) deletion at codons 1860 to … (more)
In a large Dutch family with attenuated FAP1 (see 175100), van der Luijt et al. (1996) identified a 4-bp (TTCT) deletion at codons 1860 to 1862 of the APC gene, resulting in a frameshift and an immediate stop codon. The deletion occurred in the 3-prime part of exon 15 and did not result in a stable truncated protein; only the wildtype APC protein was detected in an affected individual. The phenotype in this family showed marked variability in number of polyps (ranging from 0 to more than 100) and relatively late age at cancer onset (mean 56 years). None of the patients had desmoid tumors. Van der Luijt et al. (1996) hypothesized that the milder phenotype in this family was due to haploinsufficiency of a normal APC protein and absence of a truncated APC protein with a possible dominant-negative effect. (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 |
Germline mutations in APC and MUTYH are responsible for the majority of families with attenuated familial adenomatous polyposis. | Nielsen M | Clinical genetics | 2007 | PMID: 17489848 |
Variable phenotype of familial adenomatous polyposis in pedigrees with 3' mutation in the APC gene. | Brensinger JD | Gut | 1998 | PMID: 9824584 |
Germline mutations in the 3' part of APC exon 15 do not result in truncated proteins and are associated with attenuated adenomatous polyposis coli. | van der Luijt RB | Human genetics | 1996 | PMID: 8931709 |
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 rs587776520 ...
HelpRecord last updated Feb 20, 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.