NM_000038.6(APC):c.7720C>A (p.Leu2574Ile) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 3, 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:: RCV000217741.4

Allele description [Variation Report for NM_000038.6(APC):c.7720C>A (p.Leu2574Ile)]

NM_000038.6(APC):c.7720C>A (p.Leu2574Ile)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

5q22.2

Genomic location:

Preferred name:

NM_000038.6(APC):c.7720C>A (p.Leu2574Ile)

HGVS:

NC_000005.10:g.112843314C>A
NG_008481.4:g.155794C>A
NM_000038.6:c.7720C>AMANE SELECT
NM_001127510.3:c.7720C>A
NM_001127511.3:c.7666C>A
NM_001354895.2:c.7720C>A
NM_001354896.2:c.7774C>A
NM_001354897.2:c.7750C>A
NM_001354898.2:c.7645C>A
NM_001354899.2:c.7636C>A
NM_001354900.2:c.7597C>A
NM_001354901.2:c.7543C>A
NM_001354902.2:c.7447C>A
NM_001354903.2:c.7417C>A
NM_001354904.2:c.7342C>A
NM_001354905.2:c.7240C>A
NM_001354906.2:c.6871C>A
NP_000029.2:p.Leu2574Ile
NP_001120982.1:p.Leu2574Ile
NP_001120983.2:p.Leu2556Ile
NP_001341824.1:p.Leu2574Ile
NP_001341825.1:p.Leu2592Ile
NP_001341826.1:p.Leu2584Ile
NP_001341827.1:p.Leu2549Ile
NP_001341828.1:p.Leu2546Ile
NP_001341829.1:p.Leu2533Ile
NP_001341830.1:p.Leu2515Ile
NP_001341831.1:p.Leu2483Ile
NP_001341832.1:p.Leu2473Ile
NP_001341833.1:p.Leu2448Ile
NP_001341834.1:p.Leu2414Ile
NP_001341835.1:p.Leu2291Ile
LRG_130:g.155794C>A
NC_000005.9:g.112179011C>A
NM_000038.5:c.7720C>A

Protein change:

L2291I

Links:

dbSNP: rs876659753

NCBI 1000 Genomes Browser:

rs876659753

Molecular consequence:

NM_000038.6:c.7720C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001127510.3:c.7720C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001127511.3:c.7666C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354895.2:c.7720C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354896.2:c.7774C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354897.2:c.7750C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354898.2:c.7645C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354899.2:c.7636C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354900.2:c.7597C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354901.2:c.7543C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354902.2:c.7447C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354903.2:c.7417C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354904.2:c.7342C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354905.2:c.7240C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354906.2:c.6871C>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000276553	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (May 3, 2024)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000276553

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(May 3, 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, SCV000276553.8

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

Description

The p.L2574I variant (also known as c.7720C>A), located in coding exon 15 of the APC gene, results from a C to A substitution at nucleotide position 7720. The leucine at codon 2574 is replaced by isoleucine, an amino acid with highly similar properties. Missense alterations in APC are not a common cause of disease (Spier I et al. Genet Med. 2024 Feb;26(2):100992). This amino acid position is highly conserved in available vertebrate species. In addition, in silico predictors for this gene do not accurately predict pathogenicity. Based on the available evidence, the clinical significance of this variant remains unclear.

#	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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