NM_000038.6(APC):c.6727A>G (p.Thr2243Ala) AND Familial adenomatous polyposis 1

delete

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 18, 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:: RCV003537234.1

Allele description

NM_000038.6(APC):c.6727A>G (p.Thr2243Ala)

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.6727A>G (p.Thr2243Ala)

HGVS:

NC_000005.10:g.112842321A>G
NG_008481.4:g.154801A>G
NM_000038.6:c.6727A>GMANE SELECT
NM_001127510.3:c.6727A>G
NM_001127511.3:c.6673A>G
NM_001354895.2:c.6727A>G
NM_001354896.2:c.6781A>G
NM_001354897.2:c.6757A>G
NM_001354898.2:c.6652A>G
NM_001354899.2:c.6643A>G
NM_001354900.2:c.6604A>G
NM_001354901.2:c.6550A>G
NM_001354902.2:c.6454A>G
NM_001354903.2:c.6424A>G
NM_001354904.2:c.6349A>G
NM_001354905.2:c.6247A>G
NM_001354906.2:c.5878A>G
NP_000029.2:p.Thr2243Ala
NP_001120982.1:p.Thr2243Ala
NP_001120983.2:p.Thr2225Ala
NP_001341824.1:p.Thr2243Ala
NP_001341825.1:p.Thr2261Ala
NP_001341826.1:p.Thr2253Ala
NP_001341827.1:p.Thr2218Ala
NP_001341828.1:p.Thr2215Ala
NP_001341829.1:p.Thr2202Ala
NP_001341830.1:p.Thr2184Ala
NP_001341831.1:p.Thr2152Ala
NP_001341832.1:p.Thr2142Ala
NP_001341833.1:p.Thr2117Ala
NP_001341834.1:p.Thr2083Ala
NP_001341835.1:p.Thr1960Ala
LRG_130:g.154801A>G
NC_000005.9:g.112178018A>G
NM_000038.5:c.6727A>G

Protein change:

T1960A

Links:

dbSNP: rs773539706

NCBI 1000 Genomes Browser:

rs773539706

Molecular consequence:

NM_000038.6:c.6727A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001127510.3:c.6727A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001127511.3:c.6673A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354895.2:c.6727A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354896.2:c.6781A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354897.2:c.6757A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354898.2:c.6652A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354899.2:c.6643A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354900.2:c.6604A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354901.2:c.6550A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354902.2:c.6454A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354903.2:c.6424A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354904.2:c.6349A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354905.2:c.6247A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354906.2:c.5878A>G - 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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Rattus norvegicus cytoplasmic polyadenylation element binding protein 4 (Cpeb4),...
Rattus norvegicus cytoplasmic polyadenylation element binding protein 4 (Cpeb4), mRNA
gi|157819510|ref|NM_001106992.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000833711	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 18, 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

SCV000833711

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 18, 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, SCV000833711.5

#	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 threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 2243 of the APC protein (p.Thr2243Ala). This variant is present in population databases (rs773539706, gnomAD 0.007%). 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: 489485). 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

ClinVar

Relating variation to medicine