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NM_000038.6(APC):c.7772_7773del (p.His2591fs) AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
May 16, 2022
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV002413917.10

Allele description [Variation Report for NM_000038.6(APC):c.7772_7773del (p.His2591fs)]

NM_000038.6(APC):c.7772_7773del (p.His2591fs)

Gene:
APC:APC regulator of WNT signaling pathway [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
5q22.2
Genomic location:
Preferred name:
NM_000038.6(APC):c.7772_7773del (p.His2591fs)
HGVS:
  • NC_000005.10:g.112843366_112843367del
  • NG_008481.4:g.155846_155847del
  • NM_000038.6:c.7772_7773delMANE SELECT
  • NM_001127510.3:c.7772_7773del
  • NM_001127511.3:c.7718_7719del
  • NM_001354895.2:c.7772_7773del
  • NM_001354896.2:c.7826_7827del
  • NM_001354897.2:c.7802_7803del
  • NM_001354898.2:c.7697_7698del
  • NM_001354899.2:c.7688_7689del
  • NM_001354900.2:c.7649_7650del
  • NM_001354901.2:c.7595_7596del
  • NM_001354902.2:c.7499_7500del
  • NM_001354903.2:c.7469_7470del
  • NM_001354904.2:c.7394_7395del
  • NM_001354905.2:c.7292_7293del
  • NM_001354906.2:c.6923_6924del
  • NP_000029.2:p.His2591fs
  • NP_001120982.1:p.His2591fs
  • NP_001120983.2:p.His2573fs
  • NP_001341824.1:p.His2591fs
  • NP_001341825.1:p.His2609fs
  • NP_001341826.1:p.His2601fs
  • NP_001341827.1:p.His2566fs
  • NP_001341828.1:p.His2563fs
  • NP_001341829.1:p.His2550fs
  • NP_001341830.1:p.His2532fs
  • NP_001341831.1:p.His2500fs
  • NP_001341832.1:p.His2490fs
  • NP_001341833.1:p.His2465fs
  • NP_001341834.1:p.His2431fs
  • NP_001341835.1:p.His2308fs
  • LRG_130:g.155846_155847del
  • NC_000005.9:g.112179063_112179064del
  • NM_000038.5:c.7772_7773delAT
Protein change:
H2308fs
Links:
dbSNP: rs2149993527
NCBI 1000 Genomes Browser:
rs2149993527
Molecular consequence:
  • NM_000038.6:c.7772_7773del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001127510.3:c.7772_7773del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001127511.3:c.7718_7719del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354895.2:c.7772_7773del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354896.2:c.7826_7827del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354897.2:c.7802_7803del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354898.2:c.7697_7698del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354899.2:c.7688_7689del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354900.2:c.7649_7650del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354901.2:c.7595_7596del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354902.2:c.7499_7500del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354903.2:c.7469_7470del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354904.2:c.7394_7395del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354905.2:c.7292_7293del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354906.2:c.6923_6924del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002668965Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Jan 8, 2018) 		germlineclinical testing

Citation Link,

SCV004357708Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(May 16, 2022) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Adenomatous polyposis coli (APC): a multi-functional tumor suppressor gene.

Aoki K, Taketo MM.

J Cell Sci. 2007 Oct 1;120(Pt 19):3327-35. Review.

PubMed [citation]
PMID:
17881494

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Ambry Genetics, SCV002668965.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The c.7772_7773delAT pathogenic mutation, located in coding exon 15 of the APC gene, results from a deletion of two nucleotides at nucleotide positions 7772 to 7773, causing a translational frameshift with a predicted alternate stop codon (p.H2591Rfs*11). This alteration is expected to result in loss of function by premature protein truncation. As such, this alteration is interpreted as a disease-causing mutation.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Color Diagnostics, LLC DBA Color Health, SCV004357708.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This variant deletes 2 nucleotides in exon 16 of the APC gene, creating a frameshift and premature translation stop signal in the last coding exon. This mutant transcript is predicted to escape nonsense-mediated decay and be expressed as a truncated protein. Although functional studies have not been reported, this variant is expected to disrupt the EB1-, and HDLG-binding sites (PMID: 17881494). To our knowledge, this variant has not been reported in individuals affected with hereditary cancer in the literature. Truncating variants occurring downstream of this variant are known to be disease-causing (ClinVar variation ID: 486770, 956814, 265577, 844610). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of APC function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 3, 2024