NM_000038.6(APC):c.7558G>A (p.Gly2520Arg) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jun 7, 2023
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:: RCV000167413.7

Allele description [Variation Report for NM_000038.6(APC):c.7558G>A (p.Gly2520Arg)]

NM_000038.6(APC):c.7558G>A (p.Gly2520Arg)

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.7558G>A (p.Gly2520Arg)

HGVS:

NC_000005.10:g.112843152G>A
NG_008481.4:g.155632G>A
NM_000038.6:c.7558G>AMANE SELECT
NM_001127510.3:c.7558G>A
NM_001127511.3:c.7504G>A
NM_001354895.2:c.7558G>A
NM_001354896.2:c.7612G>A
NM_001354897.2:c.7588G>A
NM_001354898.2:c.7483G>A
NM_001354899.2:c.7474G>A
NM_001354900.2:c.7435G>A
NM_001354901.2:c.7381G>A
NM_001354902.2:c.7285G>A
NM_001354903.2:c.7255G>A
NM_001354904.2:c.7180G>A
NM_001354905.2:c.7078G>A
NM_001354906.2:c.6709G>A
NP_000029.2:p.Gly2520Arg
NP_001120982.1:p.Gly2520Arg
NP_001120983.2:p.Gly2502Arg
NP_001341824.1:p.Gly2520Arg
NP_001341825.1:p.Gly2538Arg
NP_001341826.1:p.Gly2530Arg
NP_001341827.1:p.Gly2495Arg
NP_001341828.1:p.Gly2492Arg
NP_001341829.1:p.Gly2479Arg
NP_001341830.1:p.Gly2461Arg
NP_001341831.1:p.Gly2429Arg
NP_001341832.1:p.Gly2419Arg
NP_001341833.1:p.Gly2394Arg
NP_001341834.1:p.Gly2360Arg
NP_001341835.1:p.Gly2237Arg
LRG_130:g.155632G>A
NC_000005.9:g.112178849G>A
NM_000038.5:c.7558G>A
p.G2520R

Protein change:

G2237R

Links:

dbSNP: rs746138566

NCBI 1000 Genomes Browser:

rs746138566

Molecular consequence:

NM_000038.6:c.7558G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001127510.3:c.7558G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001127511.3:c.7504G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354895.2:c.7558G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354896.2:c.7612G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354897.2:c.7588G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354898.2:c.7483G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354899.2:c.7474G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354900.2:c.7435G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354901.2:c.7381G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354902.2:c.7285G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354903.2:c.7255G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354904.2:c.7180G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354905.2:c.7078G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354906.2:c.6709G>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

Recent activity

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DC106908 Yamamoto/Hyodo-Miura NIBB/NBRP Xenopus DMZ pCS2p+ cDNA library Xenopus ...
DC106908 Yamamoto/Hyodo-Miura NIBB/NBRP Xenopus DMZ pCS2p+ cDNA library Xenopus laevis cDNA clone xl243n03 5', mRNA sequence
gi|119066552|gnl|dbEST|43337063|dbj 6908.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000218268	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Jun 7, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV001353301	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (May 26, 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

SCV000218268

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Jun 7, 2023)

germline

clinical testing

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

Citation Link,

SCV001353301

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(May 26, 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

Germline Mutations in Predisposition Genes in Pediatric Cancer.

Zhang J, Walsh MF, Wu G, Edmonson MN, Gruber TA, Easton J, Hedges D, Ma X, Zhou X, Yergeau DA, Wilkinson MR, Vadodaria B, Chen X, McGee RB, Hines-Dowell S, Nuccio R, Quinn E, Shurtleff SA, Rusch M, Patel A, Becksfort JB, Wang S, et al.

N Engl J Med. 2015 Dec 10;373(24):2336-2346. doi: 10.1056/NEJMoa1508054. Epub 2015 Nov 18.

PubMed [citation]

PMID:: 26580448
PMCID:: PMC4734119

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, SCV000218268.8

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

Description

The p.G2520R variant (also known as c.7558G>A), located in coding exon 15 of the APC gene, results from a G to A substitution at nucleotide position 7558. The glycine at codon 2520 is replaced by arginine, an amino acid with dissimilar properties. This variant has been reported in 1/1120 pediatric cancer patients who underwent whole genome sequencing and/or whole-exome sequencing; this patient was diagnosed with hypodiploid acute lymphocytic leukemia (Zhang J et al. N. Engl. J. Med., 2015 Dec;373:2336-2346). 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, SCV001353301.1

#	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: Oct 20, 2024

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