NM_000038.6(APC):c.1376A>G (p.Asp459Gly) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jun 18, 2019
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:: RCV000563425.7

Allele description [Variation Report for NM_000038.6(APC):c.1376A>G (p.Asp459Gly)]

NM_000038.6(APC):c.1376A>G (p.Asp459Gly)

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.1376A>G (p.Asp459Gly)

HGVS:

NC_000005.10:g.112821959A>G
NG_008481.4:g.134439A>G
NM_000038.6:c.1376A>GMANE SELECT
NM_001127510.3:c.1376A>G
NM_001127511.3:c.1322A>G
NM_001354895.2:c.1376A>G
NM_001354896.2:c.1376A>G
NM_001354897.2:c.1406A>G
NM_001354898.2:c.1301A>G
NM_001354899.2:c.1292A>G
NM_001354900.2:c.1199A>G
NM_001354901.2:c.1199A>G
NM_001354902.2:c.1103A>G
NM_001354903.2:c.1073A>G
NM_001354904.2:c.998A>G
NM_001354905.2:c.896A>G
NM_001354906.2:c.527A>G
NP_000029.2:p.Asp459Gly
NP_001120982.1:p.Asp459Gly
NP_001120983.2:p.Asp441Gly
NP_001341824.1:p.Asp459Gly
NP_001341825.1:p.Asp459Gly
NP_001341826.1:p.Asp469Gly
NP_001341827.1:p.Asp434Gly
NP_001341828.1:p.Asp431Gly
NP_001341829.1:p.Asp400Gly
NP_001341830.1:p.Asp400Gly
NP_001341831.1:p.Asp368Gly
NP_001341832.1:p.Asp358Gly
NP_001341833.1:p.Asp333Gly
NP_001341834.1:p.Asp299Gly
NP_001341835.1:p.Asp176Gly
LRG_130:g.134439A>G
NC_000005.9:g.112157656A>G
NM_000038.5:c.1376A>G

Protein change:

D176G

Links:

dbSNP: rs1554080714

NCBI 1000 Genomes Browser:

rs1554080714

Molecular consequence:

NM_000038.6:c.1376A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001127510.3:c.1376A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001127511.3:c.1322A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354895.2:c.1376A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354896.2:c.1376A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354897.2:c.1406A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354898.2:c.1301A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354899.2:c.1292A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354900.2:c.1199A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354901.2:c.1199A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354902.2:c.1103A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354903.2:c.1073A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354904.2:c.998A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354905.2:c.896A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354906.2:c.527A>G - 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
SCV000676308	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Aug 23, 2016)	germline	clinical testing	Citation Link,
SCV000681456	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jun 18, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000676308

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Aug 23, 2016)

germline

clinical testing

Citation Link,

SCV000681456

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jun 18, 2019)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Citations

PubMed

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, SCV000676308.5

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

Description

The p.D459G variant (also known as c.1376A>G), located in coding exon 10 of the APC gene, results from an A to G substitution at nucleotide position 1376. The aspartic acid at codon 459 is replaced by glycine, an amino acid with similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6501 samples (13002 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 90000 alleles tested) in our clinical cohort. This amino acid position is highly conserved in available vertebrate species. In addition, in silico predictors for this gene do not accurately predict pathogenicity. Since supporting evidence is limited at this time, the clinical significance of this alteration 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

From Color Diagnostics, LLC DBA Color Health, SCV000681456.3

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

#	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: Sep 29, 2024

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