NM_000038.6(APC):c.7633G>A (p.Gly2545Arg) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Mar 28, 2024
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:: RCV001186390.4

Allele description [Variation Report for NM_000038.6(APC):c.7633G>A (p.Gly2545Arg)]

NM_000038.6(APC):c.7633G>A (p.Gly2545Arg)

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.7633G>A (p.Gly2545Arg)

HGVS:

NC_000005.10:g.112843227G>A
NG_008481.4:g.155707G>A
NM_000038.6:c.7633G>AMANE SELECT
NM_001127510.3:c.7633G>A
NM_001127511.3:c.7579G>A
NM_001354895.2:c.7633G>A
NM_001354896.2:c.7687G>A
NM_001354897.2:c.7663G>A
NM_001354898.2:c.7558G>A
NM_001354899.2:c.7549G>A
NM_001354900.2:c.7510G>A
NM_001354901.2:c.7456G>A
NM_001354902.2:c.7360G>A
NM_001354903.2:c.7330G>A
NM_001354904.2:c.7255G>A
NM_001354905.2:c.7153G>A
NM_001354906.2:c.6784G>A
NP_000029.2:p.Gly2545Arg
NP_001120982.1:p.Gly2545Arg
NP_001120983.2:p.Gly2527Arg
NP_001341824.1:p.Gly2545Arg
NP_001341825.1:p.Gly2563Arg
NP_001341826.1:p.Gly2555Arg
NP_001341827.1:p.Gly2520Arg
NP_001341828.1:p.Gly2517Arg
NP_001341829.1:p.Gly2504Arg
NP_001341830.1:p.Gly2486Arg
NP_001341831.1:p.Gly2454Arg
NP_001341832.1:p.Gly2444Arg
NP_001341833.1:p.Gly2419Arg
NP_001341834.1:p.Gly2385Arg
NP_001341835.1:p.Gly2262Arg
LRG_130:g.155707G>A
NC_000005.9:g.112178924G>A
NC_000005.9:g.112178924G>A
NM_000038.5:c.7633G>A

Protein change:

G2262R

Links:

dbSNP: rs1766528528

NCBI 1000 Genomes Browser:

rs1766528528

Molecular consequence:

NM_000038.6:c.7633G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001127510.3:c.7633G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001127511.3:c.7579G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354895.2:c.7633G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354896.2:c.7687G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354897.2:c.7663G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354898.2:c.7558G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354899.2:c.7549G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354900.2:c.7510G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354901.2:c.7456G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354902.2:c.7360G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354903.2:c.7330G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354904.2:c.7255G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354905.2:c.7153G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354906.2:c.6784G>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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AGENCOURT_73648971 NICHD_XGC_olfb Xenopus laevis cDNA clone IMAGE:8539104 5', mRNA sequence
gi|92060014|gnl|dbEST|37989952|gb|E 90.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001352783	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jul 9, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005141368	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Mar 28, 2024)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001352783

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jul 9, 2019)

germline

clinical testing

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

SCV005141368

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Mar 28, 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

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 Color Diagnostics, LLC DBA Color Health, SCV001352783.2

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

Description

This missense variant replaces glycine with arginine at codon 2545 of the APC protein. Computational prediction tools and conservation analyses suggest that this variant may have deleterious impact on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

#	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 Ambry Genetics, SCV005141368.1

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

Description

The p.G2545R variant (also known as c.7633G>A), located in coding exon 15 of the APC gene, results from a G to A substitution at nucleotide position 7633. The glycine at codon 2545 is replaced by arginine, an amino acid with dissimilar properties. 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 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

Last Updated: Oct 20, 2024

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