VCV001071632.10 - ClinVar

NM_000038.6(APC):c.2557G>T (p.Glu853Ter)

Germline

Classification

criteria provided, single submitter. Learn more about how ClinVar calculates review status.

Pathogenic
Pathogenic (1)

This classification is based on the single submission received

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.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000038.6(APC):c.2557G>T (p.Glu853Ter)

Variation ID: 1071632 Accession: VCV001071632.10

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 5q22.2 5: 112838151 (GRCh38) [ NCBI UCSC ] 5: 112173848 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	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	May 10, 2021	Feb 15, 2026	Apr 1, 2020

HGVS

Nucleotide	Protein	Molecular consequence
NM_000038.6:c.2557G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000029.2:p.Glu853Ter	nonsense
NM_001127510.3:c.2557G>T	NP_001120982.1:p.Glu853Ter	nonsense
NM_001127511.3:c.2503G>T	NP_001120983.2:p.Glu835Ter	nonsense
NM_001354895.2:c.2557G>T	NP_001341824.1:p.Glu853Ter	nonsense
NM_001354896.2:c.2611G>T	NP_001341825.1:p.Glu871Ter	nonsense
NM_001354897.2:c.2587G>T	NP_001341826.1:p.Glu863Ter	nonsense
NM_001354898.2:c.2482G>T	NP_001341827.1:p.Glu828Ter	nonsense
NM_001354899.2:c.2473G>T	NP_001341828.1:p.Glu825Ter	nonsense
NM_001354900.2:c.2434G>T	NP_001341829.1:p.Glu812Ter	nonsense
NM_001354901.2:c.2380G>T	NP_001341830.1:p.Glu794Ter	nonsense
NM_001354902.2:c.2284G>T	NP_001341831.1:p.Glu762Ter	nonsense
NM_001354903.2:c.2254G>T	NP_001341832.1:p.Glu752Ter	nonsense
NM_001354904.2:c.2179G>T	NP_001341833.1:p.Glu727Ter	nonsense
NM_001354905.2:c.2077G>T	NP_001341834.1:p.Glu693Ter	nonsense
NM_001354906.2:c.1708G>T	NP_001341835.1:p.Glu570Ter	nonsense
NC_000005.10:g.112838151G>T
NC_000005.9:g.112173848G>T
NG_008481.4:g.150631G>T
LRG_130:g.150631G>T

... more HGVS ... less HGVS

Protein change

E570*, E693*, E727*, E752*, E762*, E794*, E812*, E825*, E828*, E835*, E853*, E863*, E871*

Other names

Canonical SPDI

NC_000005.10:112838150:G:T

Global minor allele frequency (GMAF) Help The 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.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA16026936 dbSNP: rs876659738 VarSome

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
Gene	OMIM	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	16898	17048

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.
Familial adenomatous polyposis 1	Pathogenic (1)	criteria provided, single submitter	Apr 1, 2020	RCV002551537.12

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.	Expand all rows Collapse all rows 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.
Pathogenic (Apr 01, 2020) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Familial adenomatous polyposis 1	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001583531.6 First in ClinVar: May 10, 2021 Last updated: Feb 15, 2026	Publications: PubMed (7) PubMed: 1316610‚ 15311282‚ 17293347‚ 22135120‚ 27081525‚ 8381579‚ 9824584 Comment: show This variant is expected to disrupt the EB1 and HDLG binding sites, which mediate interactions with the cytoskeleton (PMID: 15311282, 17293347). While functional studies have not been performed to directly test the effect on APC protein function, this suggests that disruption of the C-terminal portion of the protein is functionally important. For these reasons, this variant has been classified as Pathogenic. A different truncation (p.Tyr2645Lysfs14) that lies downstream of this variant has been determined to be pathogenic (PMID: 9824584, 1316610, 27081525, 8381579, 22135120, Invitae). This suggests that deletion of this region of the APC protein is causative of disease. This variant has not been reported in the literature in individuals with APC-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the APC gene (p.Glu853). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1991 amino acids of the APC protein. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Comment:

This variant is expected to disrupt the EB1 and HDLG binding sites, which mediate interactions with the cytoskeleton (PMID: 15311282, 17293347). While functional studies have not been performed to directly test the effect on APC protein function, this suggests that disruption of the C-terminal portion of the protein is functionally important. For these reasons, this variant has been classified as Pathogenic. A different truncation (p.Tyr2645Lysfs*14) that lies downstream of this variant has been determined to be pathogenic (PMID: 9824584, 1316610, 27081525, 8381579, 22135120, Invitae). This suggests that deletion of this region of the APC protein is causative of disease. This variant has not been reported in the literature in individuals with APC-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the APC gene (p.Glu853*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1991 amino acids of the APC protein.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
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
Regulated binding of adenomatous polyposis coli protein to actin.	Moseley JB	The Journal of biological chemistry	2007	PMID: 17293347
EB1 and APC bind to mDia to stabilize microtubules downstream of Rho and promote cell migration.	Wen Y	Nature cell biology	2004	PMID: 15311282
Variable phenotype of familial adenomatous polyposis in pedigrees with 3' mutation in the APC gene.	Brensinger JD	Gut	1998	PMID: 9824584
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 rs876659738 ...

These 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 Apr 13, 2026