NM_000038.6(APC):c.7717A>G (p.Ile2573Val) AND Hereditary cancer-predisposing syndrome

Germline classification:: Conflicting interpretations of pathogenicity (4 submissions)
Last evaluated:: Mar 13, 2022
Review status:: criteria provided, conflicting classifications

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:: RCV000163980.20

Allele description [Variation Report for NM_000038.6(APC):c.7717A>G (p.Ile2573Val)]

NM_000038.6(APC):c.7717A>G (p.Ile2573Val)

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.7717A>G (p.Ile2573Val)

HGVS:

NC_000005.10:g.112843311A>G
NG_008481.4:g.155791A>G
NM_000038.6:c.7717A>GMANE SELECT
NM_001127510.3:c.7717A>G
NM_001127511.3:c.7663A>G
NM_001354895.2:c.7717A>G
NM_001354896.2:c.7771A>G
NM_001354897.2:c.7747A>G
NM_001354898.2:c.7642A>G
NM_001354899.2:c.7633A>G
NM_001354900.2:c.7594A>G
NM_001354901.2:c.7540A>G
NM_001354902.2:c.7444A>G
NM_001354903.2:c.7414A>G
NM_001354904.2:c.7339A>G
NM_001354905.2:c.7237A>G
NM_001354906.2:c.6868A>G
NP_000029.2:p.Ile2573Val
NP_001120982.1:p.Ile2573Val
NP_001120983.2:p.Ile2555Val
NP_001341824.1:p.Ile2573Val
NP_001341825.1:p.Ile2591Val
NP_001341826.1:p.Ile2583Val
NP_001341827.1:p.Ile2548Val
NP_001341828.1:p.Ile2545Val
NP_001341829.1:p.Ile2532Val
NP_001341830.1:p.Ile2514Val
NP_001341831.1:p.Ile2482Val
NP_001341832.1:p.Ile2472Val
NP_001341833.1:p.Ile2447Val
NP_001341834.1:p.Ile2413Val
NP_001341835.1:p.Ile2290Val
LRG_130t1:c.7717A>G
LRG_130:g.155791A>G
NC_000005.9:g.112179008A>G
NM_000038.4:c.7717A>G
NM_000038.5:c.7717A>G
p.I2573V

Protein change:

I2290V

Links:

dbSNP: rs145444830

NCBI 1000 Genomes Browser:

rs145444830

Molecular consequence:

NM_000038.6:c.7717A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001127510.3:c.7717A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001127511.3:c.7663A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354895.2:c.7717A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354896.2:c.7771A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354897.2:c.7747A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354898.2:c.7642A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354899.2:c.7633A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354900.2:c.7594A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354901.2:c.7540A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354902.2:c.7444A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354903.2:c.7414A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354904.2:c.7339A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354905.2:c.7237A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354906.2:c.6868A>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
SCV000214580	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely benign (Sep 20, 2018)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 18199528, 21859464, 22703879 Citation Link,
SCV000821826	GeneKor MSA	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Aug 1, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000910847	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Jun 7, 2016)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002530799	Sema4, Sema4	criteria provided, single submitter (Sema4 Curation Guidelines)	Uncertain significance (Mar 13, 2022)	germline	curation	PubMed (3) [See all records that cite these PMIDs] 18199528, 28259476, 31159747 Citation Link

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing, curation

Citations

PubMed

Messing up disorder: how do missense mutations in the tumor suppressor protein APC lead to cancer?

Minde DP, Anvarian Z, Rüdiger SG, Maurice MM.

Mol Cancer. 2011 Aug 22;10:101. doi: 10.1186/1476-4598-10-101. Review.

PubMed [citation]

PMID:: 21859464
PMCID:: PMC3170638

Secondary variants in individuals undergoing exome sequencing: screening of 572 individuals identifies high-penetrance mutations in cancer-susceptibility genes.

Johnston JJ, Rubinstein WS, Facio FM, Ng D, Singh LN, Teer JK, Mullikin JC, Biesecker LG.

Am J Hum Genet. 2012 Jul 13;91(1):97-108. doi: 10.1016/j.ajhg.2012.05.021. Epub 2012 Jun 14.

PubMed [citation]

PMID:: 22703879
PMCID:: PMC3397257

See all PubMed Citations (6)

Details of each submission

From Ambry Genetics, SCV000214580.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

#	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 GeneKor MSA, SCV000821826.1

#	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	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Color Diagnostics, LLC DBA Color Health, SCV000910847.1

#	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

From Sema4, Sema4, SCV002530799.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (3)

#	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 16, 2024

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