NM_000038.6(APC):c.7749A>C (p.Lys2583Asn) AND Familial adenomatous polyposis 1

delete

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 24, 2021
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:: RCV003650782.1

Allele description

NM_000038.6(APC):c.7749A>C (p.Lys2583Asn)

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.7749A>C (p.Lys2583Asn)

HGVS:

NC_000005.10:g.112843343A>C
NG_008481.4:g.155823A>C
NM_000038.6:c.7749A>CMANE SELECT
NM_001127510.3:c.7749A>C
NM_001127511.3:c.7695A>C
NM_001354895.2:c.7749A>C
NM_001354896.2:c.7803A>C
NM_001354897.2:c.7779A>C
NM_001354898.2:c.7674A>C
NM_001354899.2:c.7665A>C
NM_001354900.2:c.7626A>C
NM_001354901.2:c.7572A>C
NM_001354902.2:c.7476A>C
NM_001354903.2:c.7446A>C
NM_001354904.2:c.7371A>C
NM_001354905.2:c.7269A>C
NM_001354906.2:c.6900A>C
NP_000029.2:p.Lys2583Asn
NP_001120982.1:p.Lys2583Asn
NP_001120983.2:p.Lys2565Asn
NP_001341824.1:p.Lys2583Asn
NP_001341825.1:p.Lys2601Asn
NP_001341826.1:p.Lys2593Asn
NP_001341827.1:p.Lys2558Asn
NP_001341828.1:p.Lys2555Asn
NP_001341829.1:p.Lys2542Asn
NP_001341830.1:p.Lys2524Asn
NP_001341831.1:p.Lys2492Asn
NP_001341832.1:p.Lys2482Asn
NP_001341833.1:p.Lys2457Asn
NP_001341834.1:p.Lys2423Asn
NP_001341835.1:p.Lys2300Asn
LRG_130:g.155823A>C
NC_000005.9:g.112179040A>C
NM_000038.5:c.7749A>C

Protein change:

K2300N

Links:

dbSNP: rs1766556638

NCBI 1000 Genomes Browser:

rs1766556638

Molecular consequence:

NM_000038.6:c.7749A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001127510.3:c.7749A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001127511.3:c.7695A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354895.2:c.7749A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354896.2:c.7803A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354897.2:c.7779A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354898.2:c.7674A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354899.2:c.7665A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354900.2:c.7626A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354901.2:c.7572A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354902.2:c.7476A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354903.2:c.7446A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354904.2:c.7371A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354905.2:c.7269A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354906.2:c.6900A>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
SCV001398624	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 24, 2021)	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

SCV001398624

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 24, 2021)

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, SCV001398624.5

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

Description

This sequence change replaces lysine with asparagine at codon 2583 of the APC protein (p.Lys2583Asn). The lysine residue is highly conserved and there is a moderate physicochemical difference between lysine and asparagine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with APC-related conditions. 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

#	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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