NM_000038.6(APC):c.7621A>G (p.Ile2541Val) AND Hereditary cancer-predisposing syndrome

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: Oct 29, 2021
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:: RCV000565915.15

Allele description [Variation Report for NM_000038.6(APC):c.7621A>G (p.Ile2541Val)]

NM_000038.6(APC):c.7621A>G (p.Ile2541Val)

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.7621A>G (p.Ile2541Val)

Other names:

p.I2541V:ATC>GTC

HGVS:

NC_000005.10:g.112843215A>G
NG_008481.4:g.155695A>G
NM_000038.6:c.7621A>GMANE SELECT
NM_001127510.3:c.7621A>G
NM_001127511.3:c.7567A>G
NM_001354895.2:c.7621A>G
NM_001354896.2:c.7675A>G
NM_001354897.2:c.7651A>G
NM_001354898.2:c.7546A>G
NM_001354899.2:c.7537A>G
NM_001354900.2:c.7498A>G
NM_001354901.2:c.7444A>G
NM_001354902.2:c.7348A>G
NM_001354903.2:c.7318A>G
NM_001354904.2:c.7243A>G
NM_001354905.2:c.7141A>G
NM_001354906.2:c.6772A>G
NP_000029.2:p.Ile2541Val
NP_001120982.1:p.Ile2541Val
NP_001120983.2:p.Ile2523Val
NP_001341824.1:p.Ile2541Val
NP_001341825.1:p.Ile2559Val
NP_001341826.1:p.Ile2551Val
NP_001341827.1:p.Ile2516Val
NP_001341828.1:p.Ile2513Val
NP_001341829.1:p.Ile2500Val
NP_001341830.1:p.Ile2482Val
NP_001341831.1:p.Ile2450Val
NP_001341832.1:p.Ile2440Val
NP_001341833.1:p.Ile2415Val
NP_001341834.1:p.Ile2381Val
NP_001341835.1:p.Ile2258Val
LRG_130t1:c.7621A>G
LRG_130:g.155695A>G
NC_000005.9:g.112178912A>G
NM_000038.4:c.7621A>G
NM_000038.5:c.7621A>G

Protein change:

I2258V

Links:

dbSNP: rs587778033

NCBI 1000 Genomes Browser:

rs587778033

Molecular consequence:

NM_000038.6:c.7621A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001127510.3:c.7621A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001127511.3:c.7567A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354895.2:c.7621A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354896.2:c.7675A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354897.2:c.7651A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354898.2:c.7546A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354899.2:c.7537A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354900.2:c.7498A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354901.2:c.7444A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354902.2:c.7348A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354903.2:c.7318A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354904.2:c.7243A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354905.2:c.7141A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354906.2:c.6772A>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
SCV000667239	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely benign (Nov 8, 2018)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 18199528, 21859464, 24599579, 24728327 Citation Link,
SCV000910824	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Jun 14, 2016)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002528248	Sema4, Sema4	criteria provided, single submitter (Sema4 Curation Guidelines)	Uncertain significance (Oct 29, 2021)	germline	curation	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000667239

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely benign
(Nov 8, 2018)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link,

SCV000910824

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely benign
(Jun 14, 2016)

germline

clinical testing

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

SCV002528248

Sema4, Sema4

criteria provided, single submitter

(Sema4 Curation Guidelines)

Uncertain significance
(Oct 29, 2021)

germline

curation

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

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, 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

The UMD-APC database, a model of nation-wide knowledge base: update with data from 3,581 variations.

Grandval P, Blayau M, Buisine MP, Coulet F, Maugard C, Pinson S, Remenieras A, Tinat J, Uhrhammer N, Béroud C, Olschwang S.

Hum Mutat. 2014 May;35(5):532-6. doi: 10.1002/humu.22539. Epub 2014 Apr 7.

PubMed [citation]

PMID:: 24599579

See all PubMed Citations (5)

Details of each submission

From Ambry Genetics, SCV000667239.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

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 Color Diagnostics, LLC DBA Color Health, SCV000910824.1

#	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, SCV002528248.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	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 13, 2024

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