NM_000038.6(APC):c.7460C>T (p.Ser2487Phe) AND Familial adenomatous polyposis 1

delete

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 30, 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:: RCV003653655.1

Allele description

NM_000038.6(APC):c.7460C>T (p.Ser2487Phe)

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.7460C>T (p.Ser2487Phe)

HGVS:

NC_000005.10:g.112843054C>T
NG_008481.4:g.155534C>T
NM_000038.6:c.7460C>TMANE SELECT
NM_001127510.3:c.7460C>T
NM_001127511.3:c.7406C>T
NM_001354895.2:c.7460C>T
NM_001354896.2:c.7514C>T
NM_001354897.2:c.7490C>T
NM_001354898.2:c.7385C>T
NM_001354899.2:c.7376C>T
NM_001354900.2:c.7337C>T
NM_001354901.2:c.7283C>T
NM_001354902.2:c.7187C>T
NM_001354903.2:c.7157C>T
NM_001354904.2:c.7082C>T
NM_001354905.2:c.6980C>T
NM_001354906.2:c.6611C>T
NM_001407446.1:c.7544C>T
NM_001407447.1:c.7514C>T
NM_001407448.1:c.7514C>T
NM_001407449.1:c.7514C>T
NM_001407450.1:c.7460C>T
NM_001407451.1:c.7439C>T
NM_001407452.1:c.7430C>T
NM_001407453.1:c.7283C>T
NM_001407454.1:c.7211C>T
NM_001407455.1:c.7211C>T
NM_001407456.1:c.7211C>T
NM_001407457.1:c.7211C>T
NM_001407458.1:c.7157C>T
NM_001407459.1:c.7157C>T
NM_001407460.1:c.7157C>T
NM_001407467.1:c.7073C>T
NM_001407469.1:c.7073C>T
NM_001407470.1:c.6611C>T
NM_001407471.1:c.6308C>T
NM_001407472.1:c.6308C>T
NP_000029.2:p.Ser2487Phe
NP_000029.2:p.Ser2487Phe
NP_001120982.1:p.Ser2487Phe
NP_001120982.1:p.Ser2487Phe
NP_001120983.1:p.Ser2487Phe
NP_001120983.2:p.Ser2469Phe
NP_001341824.1:p.Ser2487Phe
NP_001341825.1:p.Ser2505Phe
NP_001341826.1:p.Ser2497Phe
NP_001341827.1:p.Ser2462Phe
NP_001341828.1:p.Ser2459Phe
NP_001341829.1:p.Ser2446Phe
NP_001341830.1:p.Ser2428Phe
NP_001341831.1:p.Ser2396Phe
NP_001341832.1:p.Ser2386Phe
NP_001341833.1:p.Ser2361Phe
NP_001341834.1:p.Ser2327Phe
NP_001341835.1:p.Ser2204Phe
NP_001394375.1:p.Ser2515Phe
NP_001394376.1:p.Ser2505Phe
NP_001394377.1:p.Ser2505Phe
NP_001394378.1:p.Ser2505Phe
NP_001394379.1:p.Ser2487Phe
NP_001394380.1:p.Ser2480Phe
NP_001394381.1:p.Ser2477Phe
NP_001394382.1:p.Ser2428Phe
NP_001394383.1:p.Ser2404Phe
NP_001394384.1:p.Ser2404Phe
NP_001394385.1:p.Ser2404Phe
NP_001394386.1:p.Ser2404Phe
NP_001394387.1:p.Ser2386Phe
NP_001394388.1:p.Ser2386Phe
NP_001394389.1:p.Ser2386Phe
NP_001394396.1:p.Ser2358Phe
NP_001394398.1:p.Ser2358Phe
NP_001394399.1:p.Ser2204Phe
NP_001394400.1:p.Ser2103Phe
NP_001394401.1:p.Ser2103Phe
LRG_130t1:c.7460C>T
LRG_130t2:c.7460C>T
LRG_130t3:c.7460C>T
LRG_130:g.155534C>T
LRG_130p1:p.Ser2487Phe
LRG_130p2:p.Ser2487Phe
LRG_130p3:p.Ser2487Phe
NC_000005.9:g.112178751C>T
NM_000038.4:c.7460C>T
NM_001127510.1:c.7460C>T
NM_001127511.1:c.7460C>T
NR_176365.1:n.7295C>T
NR_176366.1:n.7714C>T

Protein change:

S2103F

Molecular consequence:

NM_000038.6:c.7460C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001127510.3:c.7460C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001127511.3:c.7406C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354895.2:c.7460C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354896.2:c.7514C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354897.2:c.7490C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354898.2:c.7385C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354899.2:c.7376C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354900.2:c.7337C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354901.2:c.7283C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354902.2:c.7187C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354903.2:c.7157C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354904.2:c.7082C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354905.2:c.6980C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354906.2:c.6611C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407446.1:c.7544C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407447.1:c.7514C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407448.1:c.7514C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407449.1:c.7514C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407450.1:c.7460C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407451.1:c.7439C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407452.1:c.7430C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407453.1:c.7283C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407454.1:c.7211C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407455.1:c.7211C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407456.1:c.7211C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407457.1:c.7211C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407458.1:c.7157C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407459.1:c.7157C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407460.1:c.7157C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407467.1:c.7073C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407469.1:c.7073C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407470.1:c.6611C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407471.1:c.6308C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407472.1:c.6308C>T - 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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Piso0_002670 [Millerozyma farinosa CBS 7064]
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gi|359381523|emb|CCE81982.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003472709	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 30, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 20233475, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003472709

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 30, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

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

Germline Missense Changes in the APC Gene and Their Relationship to Disease.

Scott RJ, Crooks R, Rose L, Attia J, Thakkinstian A, Thomas L, Spigelman AD, Meldrum CJ.

Hered Cancer Clin Pract. 2004 May 15;2(2):81-91. doi: 10.1186/1897-4287-2-2-81.

PubMed [citation]

PMID:: 20233475
PMCID:: PMC2839999

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, SCV003472709.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 2487 of the APC protein (p.Ser2487Phe). This variant is present in population databases (rs778636967, gnomAD 0.003%). This missense change has been observed in individual(s) with familial adenomatous polyposis (PMID: 20233475). This variant is also known as 7406 C>T(S2469F). ClinVar contains an entry for this variant (Variation ID: 2159583). 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. 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 9, 2024

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Relating variation to medicine