NM_000038.6(APC):c.7769A>C (p.Lys2590Thr) AND Familial adenomatous polyposis 1

delete

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 20, 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:: RCV003743864.1

Allele description

NM_000038.6(APC):c.7769A>C (p.Lys2590Thr)

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.7769A>C (p.Lys2590Thr)

HGVS:

NC_000005.10:g.112843363A>C
NG_008481.4:g.155843A>C
NM_000038.6:c.7769A>CMANE SELECT
NM_001127510.3:c.7769A>C
NM_001127511.3:c.7715A>C
NM_001354895.2:c.7769A>C
NM_001354896.2:c.7823A>C
NM_001354897.2:c.7799A>C
NM_001354898.2:c.7694A>C
NM_001354899.2:c.7685A>C
NM_001354900.2:c.7646A>C
NM_001354901.2:c.7592A>C
NM_001354902.2:c.7496A>C
NM_001354903.2:c.7466A>C
NM_001354904.2:c.7391A>C
NM_001354905.2:c.7289A>C
NM_001354906.2:c.6920A>C
NM_001407446.1:c.7853A>C
NM_001407447.1:c.7823A>C
NM_001407448.1:c.7823A>C
NM_001407449.1:c.7823A>C
NM_001407450.1:c.7769A>C
NM_001407451.1:c.7748A>C
NM_001407452.1:c.7739A>C
NM_001407453.1:c.7592A>C
NM_001407454.1:c.7520A>C
NM_001407455.1:c.7520A>C
NM_001407456.1:c.7520A>C
NM_001407457.1:c.7520A>C
NM_001407458.1:c.7466A>C
NM_001407459.1:c.7466A>C
NM_001407460.1:c.7466A>C
NM_001407467.1:c.7382A>C
NM_001407469.1:c.7382A>C
NM_001407470.1:c.6920A>C
NM_001407471.1:c.6617A>C
NM_001407472.1:c.6617A>C
NP_000029.2:p.Lys2590Thr
NP_000029.2:p.Lys2590Thr
NP_001120982.1:p.Lys2590Thr
NP_001120982.1:p.Lys2590Thr
NP_001120983.1:p.Lys2590Thr
NP_001120983.2:p.Lys2572Thr
NP_001341824.1:p.Lys2590Thr
NP_001341825.1:p.Lys2608Thr
NP_001341826.1:p.Lys2600Thr
NP_001341827.1:p.Lys2565Thr
NP_001341828.1:p.Lys2562Thr
NP_001341829.1:p.Lys2549Thr
NP_001341830.1:p.Lys2531Thr
NP_001341831.1:p.Lys2499Thr
NP_001341832.1:p.Lys2489Thr
NP_001341833.1:p.Lys2464Thr
NP_001341834.1:p.Lys2430Thr
NP_001341835.1:p.Lys2307Thr
NP_001394375.1:p.Lys2618Thr
NP_001394376.1:p.Lys2608Thr
NP_001394377.1:p.Lys2608Thr
NP_001394378.1:p.Lys2608Thr
NP_001394379.1:p.Lys2590Thr
NP_001394380.1:p.Lys2583Thr
NP_001394381.1:p.Lys2580Thr
NP_001394382.1:p.Lys2531Thr
NP_001394383.1:p.Lys2507Thr
NP_001394384.1:p.Lys2507Thr
NP_001394385.1:p.Lys2507Thr
NP_001394386.1:p.Lys2507Thr
NP_001394387.1:p.Lys2489Thr
NP_001394388.1:p.Lys2489Thr
NP_001394389.1:p.Lys2489Thr
NP_001394396.1:p.Lys2461Thr
NP_001394398.1:p.Lys2461Thr
NP_001394399.1:p.Lys2307Thr
NP_001394400.1:p.Lys2206Thr
NP_001394401.1:p.Lys2206Thr
LRG_130t1:c.7769A>C
LRG_130t2:c.7769A>C
LRG_130t3:c.7769A>C
LRG_130:g.155843A>C
LRG_130p1:p.Lys2590Thr
LRG_130p2:p.Lys2590Thr
LRG_130p3:p.Lys2590Thr
NC_000005.9:g.112179060A>C
NM_000038.4:c.7769A>C
NM_001127510.1:c.7769A>C
NM_001127511.1:c.7769A>C
NR_176365.1:n.7604A>C
NR_176366.1:n.8023A>C

Protein change:

K2206T

Molecular consequence:

NM_000038.6:c.7769A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001127510.3:c.7769A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001127511.3:c.7715A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354895.2:c.7769A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354896.2:c.7823A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354897.2:c.7799A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354898.2:c.7694A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354899.2:c.7685A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354900.2:c.7646A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354901.2:c.7592A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354902.2:c.7496A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354903.2:c.7466A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354904.2:c.7391A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354905.2:c.7289A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354906.2:c.6920A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407446.1:c.7853A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407447.1:c.7823A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407448.1:c.7823A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407449.1:c.7823A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407450.1:c.7769A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407451.1:c.7748A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407452.1:c.7739A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407453.1:c.7592A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407454.1:c.7520A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407455.1:c.7520A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407456.1:c.7520A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407457.1:c.7520A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407458.1:c.7466A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407459.1:c.7466A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407460.1:c.7466A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407467.1:c.7382A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407469.1:c.7382A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407470.1:c.6920A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407471.1:c.6617A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407472.1:c.6617A>C - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002594658	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 20, 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

SCV002594658

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 20, 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 Invitae, SCV002594658.3

#	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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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 lysine, which is basic and polar, with threonine, which is neutral and polar, at codon 2590 of the APC protein (p.Lys2590Thr).

#	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 9, 2024

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