NM_000038.6(APC):c.7816G>A (p.Val2606Ile) AND Familial adenomatous polyposis 1

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Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 20, 2019
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV002240540.15

Allele description

NM_000038.6(APC):c.7816G>A (p.Val2606Ile)

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.7816G>A (p.Val2606Ile)

HGVS:

NC_000005.10:g.112843410G>A
NG_008481.4:g.155890G>A
NM_000038.6:c.7816G>AMANE SELECT
NM_001127510.3:c.7816G>A
NM_001127511.3:c.7762G>A
NM_001354895.2:c.7816G>A
NM_001354896.2:c.7870G>A
NM_001354897.2:c.7846G>A
NM_001354898.2:c.7741G>A
NM_001354899.2:c.7732G>A
NM_001354900.2:c.7693G>A
NM_001354901.2:c.7639G>A
NM_001354902.2:c.7543G>A
NM_001354903.2:c.7513G>A
NM_001354904.2:c.7438G>A
NM_001354905.2:c.7336G>A
NM_001354906.2:c.6967G>A
NP_000029.2:p.Val2606Ile
NP_001120982.1:p.Val2606Ile
NP_001120983.2:p.Val2588Ile
NP_001341824.1:p.Val2606Ile
NP_001341825.1:p.Val2624Ile
NP_001341826.1:p.Val2616Ile
NP_001341827.1:p.Val2581Ile
NP_001341828.1:p.Val2578Ile
NP_001341829.1:p.Val2565Ile
NP_001341830.1:p.Val2547Ile
NP_001341831.1:p.Val2515Ile
NP_001341832.1:p.Val2505Ile
NP_001341833.1:p.Val2480Ile
NP_001341834.1:p.Val2446Ile
NP_001341835.1:p.Val2323Ile
LRG_130:g.155890G>A
NC_000005.9:g.112179107G>A
NM_000038.5:c.7816G>A

Protein change:

V2323I

Links:

dbSNP: rs1766573660

NCBI 1000 Genomes Browser:

rs1766573660

Molecular consequence:

NM_000038.6:c.7816G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001127510.3:c.7816G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001127511.3:c.7762G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354895.2:c.7816G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354896.2:c.7870G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354897.2:c.7846G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354898.2:c.7741G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354899.2:c.7732G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354900.2:c.7693G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354901.2:c.7639G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354902.2:c.7543G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354903.2:c.7513G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354904.2:c.7438G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354905.2:c.7336G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354906.2:c.6967G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Familial adenomatous polyposis 1 (FAP1)
Synonyms:: POLYPOSIS, ADENOMATOUS INTESTINAL; FAMILIAL ADENOMATOUS POLYPOSIS 1, ATTENUATED; APC-Associated Polyposis Conditions
Identifiers:: MONDO: MONDO:0021056; MedGen: C2713442; OMIM: 175100

Recent activity

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DNA replication complex GINS protein PSF3 isoform b [Homo sapiens]
DNA replication complex GINS protein PSF3 isoform b [Homo sapiens]
gi|21362088|ref|NP_073607.2|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001232349	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 20, 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

SCV001232349

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 20, 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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV001232349.6

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with APC-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with isoleucine at codon 2606 of the APC protein (p.Val2606Ile). The valine residue is moderately conserved and there is a small physicochemical difference between valine and isoleucine.

#	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: Jun 2, 2024

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