NM_000038.6(APC):c.7483A>G (p.Thr2495Ala) AND Familial adenomatous polyposis 1

delete

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 19, 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:: RCV003745801.1

Allele description

NM_000038.6(APC):c.7483A>G (p.Thr2495Ala)

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.7483A>G (p.Thr2495Ala)

HGVS:

NC_000005.10:g.112843077A>G
NG_008481.4:g.155557A>G
NM_000038.6:c.7483A>GMANE SELECT
NM_001127510.3:c.7483A>G
NM_001127511.3:c.7429A>G
NM_001354895.2:c.7483A>G
NM_001354896.2:c.7537A>G
NM_001354897.2:c.7513A>G
NM_001354898.2:c.7408A>G
NM_001354899.2:c.7399A>G
NM_001354900.2:c.7360A>G
NM_001354901.2:c.7306A>G
NM_001354902.2:c.7210A>G
NM_001354903.2:c.7180A>G
NM_001354904.2:c.7105A>G
NM_001354905.2:c.7003A>G
NM_001354906.2:c.6634A>G
NM_001407446.1:c.7567A>G
NM_001407447.1:c.7537A>G
NM_001407448.1:c.7537A>G
NM_001407449.1:c.7537A>G
NM_001407450.1:c.7483A>G
NM_001407451.1:c.7462A>G
NM_001407452.1:c.7453A>G
NM_001407453.1:c.7306A>G
NM_001407454.1:c.7234A>G
NM_001407455.1:c.7234A>G
NM_001407456.1:c.7234A>G
NM_001407457.1:c.7234A>G
NM_001407458.1:c.7180A>G
NM_001407459.1:c.7180A>G
NM_001407460.1:c.7180A>G
NM_001407467.1:c.7096A>G
NM_001407469.1:c.7096A>G
NM_001407470.1:c.6634A>G
NM_001407471.1:c.6331A>G
NM_001407472.1:c.6331A>G
NP_000029.2:p.Thr2495Ala
NP_000029.2:p.Thr2495Ala
NP_001120982.1:p.Thr2495Ala
NP_001120982.1:p.Thr2495Ala
NP_001120983.1:p.Thr2495Ala
NP_001120983.2:p.Thr2477Ala
NP_001341824.1:p.Thr2495Ala
NP_001341825.1:p.Thr2513Ala
NP_001341826.1:p.Thr2505Ala
NP_001341827.1:p.Thr2470Ala
NP_001341828.1:p.Thr2467Ala
NP_001341829.1:p.Thr2454Ala
NP_001341830.1:p.Thr2436Ala
NP_001341831.1:p.Thr2404Ala
NP_001341832.1:p.Thr2394Ala
NP_001341833.1:p.Thr2369Ala
NP_001341834.1:p.Thr2335Ala
NP_001341835.1:p.Thr2212Ala
NP_001394375.1:p.Thr2523Ala
NP_001394376.1:p.Thr2513Ala
NP_001394377.1:p.Thr2513Ala
NP_001394378.1:p.Thr2513Ala
NP_001394379.1:p.Thr2495Ala
NP_001394380.1:p.Thr2488Ala
NP_001394381.1:p.Thr2485Ala
NP_001394382.1:p.Thr2436Ala
NP_001394383.1:p.Thr2412Ala
NP_001394384.1:p.Thr2412Ala
NP_001394385.1:p.Thr2412Ala
NP_001394386.1:p.Thr2412Ala
NP_001394387.1:p.Thr2394Ala
NP_001394388.1:p.Thr2394Ala
NP_001394389.1:p.Thr2394Ala
NP_001394396.1:p.Thr2366Ala
NP_001394398.1:p.Thr2366Ala
NP_001394399.1:p.Thr2212Ala
NP_001394400.1:p.Thr2111Ala
NP_001394401.1:p.Thr2111Ala
LRG_130t1:c.7483A>G
LRG_130t2:c.7483A>G
LRG_130t3:c.7483A>G
LRG_130:g.155557A>G
LRG_130p1:p.Thr2495Ala
LRG_130p2:p.Thr2495Ala
LRG_130p3:p.Thr2495Ala
NC_000005.9:g.112178774A>G
NM_000038.4:c.7483A>G
NM_001127510.1:c.7483A>G
NM_001127511.1:c.7483A>G
NR_176365.1:n.7318A>G
NR_176366.1:n.7737A>G

Protein change:

T2111A

Molecular consequence:

NM_000038.6:c.7483A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001127510.3:c.7483A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001127511.3:c.7429A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354895.2:c.7483A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354896.2:c.7537A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354897.2:c.7513A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354898.2:c.7408A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354899.2:c.7399A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354900.2:c.7360A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354901.2:c.7306A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354902.2:c.7210A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354903.2:c.7180A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354904.2:c.7105A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354905.2:c.7003A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354906.2:c.6634A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407446.1:c.7567A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407447.1:c.7537A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407448.1:c.7537A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407449.1:c.7537A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407450.1:c.7483A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407451.1:c.7462A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407452.1:c.7453A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407453.1:c.7306A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407454.1:c.7234A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407455.1:c.7234A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407456.1:c.7234A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407457.1:c.7234A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407458.1:c.7180A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407459.1:c.7180A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407460.1:c.7180A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407467.1:c.7096A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407469.1:c.7096A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407470.1:c.6634A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407471.1:c.6331A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407472.1:c.6331A>G - missense variant - [Sequence Ontology: SO:0001583]
NR_176365.1:n.7318A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176366.1:n.7737A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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
SCV004385861	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 19, 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

SCV004385861

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 19, 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, SCV004385861.1

#	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. 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 threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 2495 of the APC protein (p.Thr2495Ala).

#	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: Feb 28, 2024

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