NM_000038.6(APC):c.7692G>C (p.Trp2564Cys) AND Familial adenomatous polyposis 1

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Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 16, 2023
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:: RCV002242334.15

Allele description

NM_000038.6(APC):c.7692G>C (p.Trp2564Cys)

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.7692G>C (p.Trp2564Cys)

HGVS:

NC_000005.10:g.112843286G>C
NG_008481.4:g.155766G>C
NM_000038.6:c.7692G>CMANE SELECT
NM_001127510.3:c.7692G>C
NM_001127511.3:c.7638G>C
NM_001354895.2:c.7692G>C
NM_001354896.2:c.7746G>C
NM_001354897.2:c.7722G>C
NM_001354898.2:c.7617G>C
NM_001354899.2:c.7608G>C
NM_001354900.2:c.7569G>C
NM_001354901.2:c.7515G>C
NM_001354902.2:c.7419G>C
NM_001354903.2:c.7389G>C
NM_001354904.2:c.7314G>C
NM_001354905.2:c.7212G>C
NM_001354906.2:c.6843G>C
NP_000029.2:p.Trp2564Cys
NP_001120982.1:p.Trp2564Cys
NP_001120983.2:p.Trp2546Cys
NP_001341824.1:p.Trp2564Cys
NP_001341825.1:p.Trp2582Cys
NP_001341826.1:p.Trp2574Cys
NP_001341827.1:p.Trp2539Cys
NP_001341828.1:p.Trp2536Cys
NP_001341829.1:p.Trp2523Cys
NP_001341830.1:p.Trp2505Cys
NP_001341831.1:p.Trp2473Cys
NP_001341832.1:p.Trp2463Cys
NP_001341833.1:p.Trp2438Cys
NP_001341834.1:p.Trp2404Cys
NP_001341835.1:p.Trp2281Cys
LRG_130:g.155766G>C
NC_000005.9:g.112178983G>C

Protein change:

W2281C

Links:

dbSNP: rs1766542279

NCBI 1000 Genomes Browser:

rs1766542279

Molecular consequence:

NM_000038.6:c.7692G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001127510.3:c.7692G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001127511.3:c.7638G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354895.2:c.7692G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354896.2:c.7746G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354897.2:c.7722G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354898.2:c.7617G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354899.2:c.7608G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354900.2:c.7569G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354901.2:c.7515G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354902.2:c.7419G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354903.2:c.7389G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354904.2:c.7314G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354905.2:c.7212G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354906.2:c.6843G>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

Recent activity

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Homo sapiens synuclein, alpha interacting protein (SNCAIP), transcript variant 1...
Homo sapiens synuclein, alpha interacting protein (SNCAIP), transcript variant 1, mRNA
gi|76563939|ref|NM_005460.2|

Nucleotide
RecName: Full=Inactive phospholipase D5; Short=Inactive PLD 5; AltName: Full=Ina...
RecName: Full=Inactive phospholipase D5; Short=Inactive PLD 5; AltName: Full=Inactive choline phosphatase 5; AltName: Full=Inactive phosphatidylcholine-hydrolyzing phospholipase D5; AltName: Full=PLDc
gi|152112223|sp|Q8N7P1.2|PLD5_HUMAN

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001537403	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 16, 2023)	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

SCV001537403

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 16, 2023)

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, SCV001537403.5

#	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 tryptophan, which is neutral and slightly polar, with cysteine, which is neutral and slightly polar, at codon 2564 of the APC protein (p.Trp2564Cys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 1039868). 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 with a negative predictive value of 95%. 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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