NM_000038.6(APC):c.7681G>A (p.Val2561Ile) AND Familial adenomatous polyposis 1

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 28, 2022
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:: RCV003099713.3

Allele description [Variation Report for NM_000038.6(APC):c.7681G>A (p.Val2561Ile)]

NM_000038.6(APC):c.7681G>A (p.Val2561Ile)

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.7681G>A (p.Val2561Ile)

HGVS:

NC_000005.10:g.112843275G>A
NG_008481.4:g.155755G>A
NM_000038.6:c.7681G>AMANE SELECT
NM_001127510.3:c.7681G>A
NM_001127511.3:c.7627G>A
NM_001354895.2:c.7681G>A
NM_001354896.2:c.7735G>A
NM_001354897.2:c.7711G>A
NM_001354898.2:c.7606G>A
NM_001354899.2:c.7597G>A
NM_001354900.2:c.7558G>A
NM_001354901.2:c.7504G>A
NM_001354902.2:c.7408G>A
NM_001354903.2:c.7378G>A
NM_001354904.2:c.7303G>A
NM_001354905.2:c.7201G>A
NM_001354906.2:c.6832G>A
NM_001407446.1:c.7765G>A
NM_001407447.1:c.7735G>A
NM_001407448.1:c.7735G>A
NM_001407449.1:c.7735G>A
NM_001407450.1:c.7681G>A
NM_001407451.1:c.7660G>A
NM_001407452.1:c.7651G>A
NM_001407453.1:c.7504G>A
NM_001407454.1:c.7432G>A
NM_001407455.1:c.7432G>A
NM_001407456.1:c.7432G>A
NM_001407457.1:c.7432G>A
NM_001407458.1:c.7378G>A
NM_001407459.1:c.7378G>A
NM_001407460.1:c.7378G>A
NM_001407467.1:c.7294G>A
NM_001407469.1:c.7294G>A
NM_001407470.1:c.6832G>A
NM_001407471.1:c.6529G>A
NM_001407472.1:c.6529G>A
NP_000029.2:p.Val2561Ile
NP_000029.2:p.Val2561Ile
NP_001120982.1:p.Val2561Ile
NP_001120982.1:p.Val2561Ile
NP_001120983.1:p.Val2561Ile
NP_001120983.2:p.Val2543Ile
NP_001341824.1:p.Val2561Ile
NP_001341825.1:p.Val2579Ile
NP_001341826.1:p.Val2571Ile
NP_001341827.1:p.Val2536Ile
NP_001341828.1:p.Val2533Ile
NP_001341829.1:p.Val2520Ile
NP_001341830.1:p.Val2502Ile
NP_001341831.1:p.Val2470Ile
NP_001341832.1:p.Val2460Ile
NP_001341833.1:p.Val2435Ile
NP_001341834.1:p.Val2401Ile
NP_001341835.1:p.Val2278Ile
NP_001394375.1:p.Val2589Ile
NP_001394376.1:p.Val2579Ile
NP_001394377.1:p.Val2579Ile
NP_001394378.1:p.Val2579Ile
NP_001394379.1:p.Val2561Ile
NP_001394380.1:p.Val2554Ile
NP_001394381.1:p.Val2551Ile
NP_001394382.1:p.Val2502Ile
NP_001394383.1:p.Val2478Ile
NP_001394384.1:p.Val2478Ile
NP_001394385.1:p.Val2478Ile
NP_001394386.1:p.Val2478Ile
NP_001394387.1:p.Val2460Ile
NP_001394388.1:p.Val2460Ile
NP_001394389.1:p.Val2460Ile
NP_001394396.1:p.Val2432Ile
NP_001394398.1:p.Val2432Ile
NP_001394399.1:p.Val2278Ile
NP_001394400.1:p.Val2177Ile
NP_001394401.1:p.Val2177Ile
LRG_130t1:c.7681G>A
LRG_130t2:c.7681G>A
LRG_130t3:c.7681G>A
LRG_130:g.155755G>A
LRG_130p1:p.Val2561Ile
LRG_130p2:p.Val2561Ile
LRG_130p3:p.Val2561Ile
NC_000005.9:g.112178972G>A
NM_000038.4:c.7681G>A
NM_000038.5:c.7681G>A
NM_001127510.1:c.7681G>A
NM_001127511.1:c.7681G>A
NR_176365.1:n.7516G>A
NR_176366.1:n.7935G>A

Protein change:

V2177I

Molecular consequence:

NM_000038.6:c.7681G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001127510.3:c.7681G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001127511.3:c.7627G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354895.2:c.7681G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354896.2:c.7735G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354897.2:c.7711G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354898.2:c.7606G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354899.2:c.7597G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354900.2:c.7558G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354901.2:c.7504G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354902.2:c.7408G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354903.2:c.7378G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354904.2:c.7303G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354905.2:c.7201G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354906.2:c.6832G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407446.1:c.7765G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407447.1:c.7735G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407448.1:c.7735G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407449.1:c.7735G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407450.1:c.7681G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407451.1:c.7660G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407452.1:c.7651G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407453.1:c.7504G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407454.1:c.7432G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407455.1:c.7432G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407456.1:c.7432G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407457.1:c.7432G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407458.1:c.7378G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407459.1:c.7378G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407460.1:c.7378G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407467.1:c.7294G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407469.1:c.7294G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407470.1:c.6832G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407471.1:c.6529G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407472.1:c.6529G>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

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epidermal growth factor-like protein 6 precursor [Mus musculus]
epidermal growth factor-like protein 6 precursor [Mus musculus]
gi|9506563|ref|NP_062270.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003277441	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 28, 2022)	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

SCV003277441

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 28, 2022)

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV003277441.2

#	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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 2561 of the APC protein (p.Val2561Ile).

#	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 29, 2024

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