NM_000038.6(APC):c.8152_8153del (p.Leu2718fs) AND Hereditary cancer-predisposing syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Feb 29, 2024
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:: RCV004518458.1

Allele description [Variation Report for NM_000038.6(APC):c.8152_8153del (p.Leu2718fs)]

NM_000038.6(APC):c.8152_8153del (p.Leu2718fs)

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.8152_8153del (p.Leu2718fs)

HGVS:

NC_000005.10:g.112843746_112843747del
NG_008481.4:g.156226_156227del
NM_000038.6:c.8152_8153delMANE SELECT
NM_001127510.3:c.8152_8153del
NM_001127511.3:c.8098_8099del
NM_001354895.2:c.8152_8153del
NM_001354896.2:c.8206_8207del
NM_001354897.2:c.8182_8183del
NM_001354898.2:c.8077_8078del
NM_001354899.2:c.8068_8069del
NM_001354900.2:c.8029_8030del
NM_001354901.2:c.7975_7976del
NM_001354902.2:c.7879_7880del
NM_001354903.2:c.7849_7850del
NM_001354904.2:c.7774_7775del
NM_001354905.2:c.7672_7673del
NM_001354906.2:c.7303_7304del
NM_001407446.1:c.8236_8237del
NM_001407447.1:c.8206_8207del
NM_001407448.1:c.8206_8207del
NM_001407449.1:c.8206_8207del
NM_001407450.1:c.8152_8153del
NM_001407451.1:c.8131_8132del
NM_001407452.1:c.8122_8123del
NM_001407453.1:c.7975_7976del
NM_001407454.1:c.7903_7904del
NM_001407455.1:c.7903_7904del
NM_001407456.1:c.7903_7904del
NM_001407457.1:c.7903_7904del
NM_001407458.1:c.7849_7850del
NM_001407459.1:c.7849_7850del
NM_001407460.1:c.7849_7850del
NM_001407467.1:c.7765_7766del
NM_001407469.1:c.7765_7766del
NM_001407470.1:c.7303_7304del
NM_001407471.1:c.7000_7001del
NM_001407472.1:c.7000_7001del
NP_000029.2:p.Leu2718Glyfs
NP_000029.2:p.Leu2718fs
NP_001120982.1:p.Leu2718Glyfs
NP_001120982.1:p.Leu2718fs
NP_001120983.1:p.Leu2718Glyfs
NP_001120983.2:p.Leu2700fs
NP_001341824.1:p.Leu2718fs
NP_001341825.1:p.Leu2736fs
NP_001341826.1:p.Leu2728fs
NP_001341827.1:p.Leu2693fs
NP_001341828.1:p.Leu2690fs
NP_001341829.1:p.Leu2677fs
NP_001341830.1:p.Leu2659fs
NP_001341831.1:p.Leu2627fs
NP_001341832.1:p.Leu2617fs
NP_001341833.1:p.Leu2592fs
NP_001341834.1:p.Leu2558fs
NP_001341835.1:p.Leu2435fs
NP_001394375.1:p.Leu2746fs
NP_001394376.1:p.Leu2736fs
NP_001394377.1:p.Leu2736fs
NP_001394378.1:p.Leu2736fs
NP_001394379.1:p.Leu2718fs
NP_001394380.1:p.Leu2711fs
NP_001394381.1:p.Leu2708fs
NP_001394382.1:p.Leu2659fs
NP_001394383.1:p.Leu2635fs
NP_001394384.1:p.Leu2635fs
NP_001394385.1:p.Leu2635fs
NP_001394386.1:p.Leu2635fs
NP_001394387.1:p.Leu2617fs
NP_001394388.1:p.Leu2617fs
NP_001394389.1:p.Leu2617fs
NP_001394396.1:p.Leu2589fs
NP_001394398.1:p.Leu2589fs
NP_001394399.1:p.Leu2435fs
NP_001394400.1:p.Leu2334fs
NP_001394401.1:p.Leu2334fs
LRG_130t1:c.8152_8153del
LRG_130t2:c.8152_8153del
LRG_130t3:c.8152_8153del
LRG_130:g.156226_156227del
LRG_130p1:p.Leu2718Glyfs
LRG_130p2:p.Leu2718Glyfs
LRG_130p3:p.Leu2718Glyfs
NC_000005.9:g.112179443_112179444del
NM_000038.4:c.8152_8153delTT
NM_000038.5:c.8152_8153delTT
NM_001127510.1:c.8152_8153delTT
NM_001127511.1:c.8152_8153delTT
NR_176365.1:n.7987_7988del
NR_176366.1:n.8406_8407del

Protein change:

L2334fs

Molecular consequence:

NM_000038.6:c.8152_8153del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001127510.3:c.8152_8153del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001127511.3:c.8098_8099del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354895.2:c.8152_8153del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354896.2:c.8206_8207del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354897.2:c.8182_8183del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354898.2:c.8077_8078del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354899.2:c.8068_8069del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354900.2:c.8029_8030del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354901.2:c.7975_7976del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354902.2:c.7879_7880del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354903.2:c.7849_7850del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354904.2:c.7774_7775del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354905.2:c.7672_7673del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354906.2:c.7303_7304del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407446.1:c.8236_8237del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407447.1:c.8206_8207del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407448.1:c.8206_8207del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407449.1:c.8206_8207del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407450.1:c.8152_8153del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407451.1:c.8131_8132del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407452.1:c.8122_8123del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407453.1:c.7975_7976del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407454.1:c.7903_7904del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407455.1:c.7903_7904del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407456.1:c.7903_7904del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407457.1:c.7903_7904del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407458.1:c.7849_7850del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407459.1:c.7849_7850del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407460.1:c.7849_7850del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407467.1:c.7765_7766del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407469.1:c.7765_7766del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407470.1:c.7303_7304del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407471.1:c.7000_7001del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407472.1:c.7000_7001del - frameshift variant - [Sequence Ontology: SO:0001589]
NR_176365.1:n.7987_7988del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176366.1:n.8406_8407del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005035452	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Feb 29, 2024)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005035452

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Feb 29, 2024)

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, SCV005035452.1

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

Description

The c.8152_8153delTT variant, located in coding exon 15 of the APC gene, results from a deletion of two nucleotides at nucleotide positions 8152 to 8153, causing a translational frameshift with a predicted alternate stop codon (p.L2718Gfs*14). This alteration occurs at the 3' terminus of theAPC gene, is not expected to trigger nonsense-mediated mRNA decay, and only impacts the last 127 amino acids of the protein. However, premature stop codons are typically deleterious in nature and the impacted region is critical for protein function (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic.

#	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: May 7, 2024

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