NM_000038.6(APC):c.7754A>C (p.Lys2585Thr) AND Familial adenomatous polyposis 1

delete

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 29, 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:: RCV003743653.1

Allele description

NM_000038.6(APC):c.7754A>C (p.Lys2585Thr)

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.7754A>C (p.Lys2585Thr)

HGVS:

NC_000005.10:g.112843348A>C
NG_008481.4:g.155828A>C
NM_000038.6:c.7754A>CMANE SELECT
NM_001127510.3:c.7754A>C
NM_001127511.3:c.7700A>C
NM_001354895.2:c.7754A>C
NM_001354896.2:c.7808A>C
NM_001354897.2:c.7784A>C
NM_001354898.2:c.7679A>C
NM_001354899.2:c.7670A>C
NM_001354900.2:c.7631A>C
NM_001354901.2:c.7577A>C
NM_001354902.2:c.7481A>C
NM_001354903.2:c.7451A>C
NM_001354904.2:c.7376A>C
NM_001354905.2:c.7274A>C
NM_001354906.2:c.6905A>C
NP_000029.2:p.Lys2585Thr
NP_001120982.1:p.Lys2585Thr
NP_001120983.2:p.Lys2567Thr
NP_001341824.1:p.Lys2585Thr
NP_001341825.1:p.Lys2603Thr
NP_001341826.1:p.Lys2595Thr
NP_001341827.1:p.Lys2560Thr
NP_001341828.1:p.Lys2557Thr
NP_001341829.1:p.Lys2544Thr
NP_001341830.1:p.Lys2526Thr
NP_001341831.1:p.Lys2494Thr
NP_001341832.1:p.Lys2484Thr
NP_001341833.1:p.Lys2459Thr
NP_001341834.1:p.Lys2425Thr
NP_001341835.1:p.Lys2302Thr
LRG_130:g.155828A>C
NC_000005.9:g.112179045A>C
NM_000038.5:c.7754A>C

Protein change:

K2302T

Links:

dbSNP: rs876658884

NCBI 1000 Genomes Browser:

rs876658884

Molecular consequence:

NM_000038.6:c.7754A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001127510.3:c.7754A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001127511.3:c.7700A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354895.2:c.7754A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354896.2:c.7808A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354897.2:c.7784A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354898.2:c.7679A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354899.2:c.7670A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354900.2:c.7631A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354901.2:c.7577A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354902.2:c.7481A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354903.2:c.7451A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354904.2:c.7376A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354905.2:c.7274A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354906.2:c.6905A>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
SCV000647729	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 29, 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

SCV000647729

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 29, 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, SCV000647729.6

#	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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt APC protein function. ClinVar contains an entry for this variant (Variation ID: 230982). 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 2585 of the APC protein (p.Lys2585Thr).

#	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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Relating variation to medicine