NM_000038.6(APC):c.7467_7468dup (p.Asp2490fs) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 7, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV002395217.2

Allele description [Variation Report for NM_000038.6(APC):c.7467_7468dup (p.Asp2490fs)]

NM_000038.6(APC):c.7467_7468dup (p.Asp2490fs)

Gene:

APC:APC regulator of WNT signaling pathway [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

5q22.2

Genomic location:

Preferred name:

NM_000038.6(APC):c.7467_7468dup (p.Asp2490fs)

HGVS:

NC_000005.10:g.112843061_112843062dup
NG_008481.4:g.155541_155542dup
NM_000038.6:c.7467_7468dupMANE SELECT
NM_001127510.3:c.7467_7468dup
NM_001127511.3:c.7413_7414dup
NM_001354895.2:c.7467_7468dup
NM_001354896.2:c.7521_7522dup
NM_001354897.2:c.7497_7498dup
NM_001354898.2:c.7392_7393dup
NM_001354899.2:c.7383_7384dup
NM_001354900.2:c.7344_7345dup
NM_001354901.2:c.7290_7291dup
NM_001354902.2:c.7194_7195dup
NM_001354903.2:c.7164_7165dup
NM_001354904.2:c.7089_7090dup
NM_001354905.2:c.6987_6988dup
NM_001354906.2:c.6618_6619dup
NP_000029.2:p.Asp2490fs
NP_001120982.1:p.Asp2490fs
NP_001120983.2:p.Asp2472fs
NP_001341824.1:p.Asp2490fs
NP_001341825.1:p.Asp2508fs
NP_001341826.1:p.Asp2500fs
NP_001341827.1:p.Asp2465fs
NP_001341828.1:p.Asp2462fs
NP_001341829.1:p.Asp2449fs
NP_001341830.1:p.Asp2431fs
NP_001341831.1:p.Asp2399fs
NP_001341832.1:p.Asp2389fs
NP_001341833.1:p.Asp2364fs
NP_001341834.1:p.Asp2330fs
NP_001341835.1:p.Asp2207fs
LRG_130:g.155541_155542dup
NC_000005.9:g.112178757_112178758insTG
NC_000005.9:g.112178758_112178759dup
NM_000038.5:c.7467_7468dup
NM_000038.5:c.7467_7468dupTG
p.Asp2490Valfs*27

Protein change:

D2207fs

Links:

dbSNP: rs1554088383

NCBI 1000 Genomes Browser:

rs1554088383

Molecular consequence:

NM_000038.6:c.7467_7468dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001127510.3:c.7467_7468dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001127511.3:c.7413_7414dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354895.2:c.7467_7468dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354896.2:c.7521_7522dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354897.2:c.7497_7498dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354898.2:c.7392_7393dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354899.2:c.7383_7384dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354900.2:c.7344_7345dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354901.2:c.7290_7291dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354902.2:c.7194_7195dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354903.2:c.7164_7165dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354904.2:c.7089_7090dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354905.2:c.6987_6988dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354906.2:c.6618_6619dup - 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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60S ribosomal protein eL41 [Schizosaccharomyces pombe]
60S ribosomal protein eL41 [Schizosaccharomyces pombe]
gi|19114862|ref|NP_593950.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002674140	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Jun 7, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002674140

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Jun 7, 2022)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From Ambry Genetics, SCV002674140.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The c.7467_7468dupTG pathogenic mutation, located in coding exon 15 of the APC gene, results from a duplication of TG at nucleotide position 7467, causing a translational frameshift with a predicted alternate stop codon (p.D2490Vfs*27). This alteration occurs at the 3' terminus of the APC gene, is not expected to trigger nonsense-mediated mRNA decay, and impacts the last 354 amino acids of the protein. However, premature stop codons are typically deleterious in nature and the impacted region is critical for protein function and a significant portion of the protein is affected (Ambry internal data). This alteration has been observed in at least one individual with a personal and/or family history that is consistent with APC-related disease (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 26, 2024

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