NM_000038.6(APC):c.7663T>C (p.Ser2555Pro) AND Familial adenomatous polyposis 1

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 26, 2022
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:: RCV003772657.2

Allele description [Variation Report for NM_000038.6(APC):c.7663T>C (p.Ser2555Pro)]

NM_000038.6(APC):c.7663T>C (p.Ser2555Pro)

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.7663T>C (p.Ser2555Pro)

HGVS:

NC_000005.10:g.112843257T>C
NG_008481.4:g.155737T>C
NM_000038.5:c.7663T>C
NM_000038.6:c.7663T>CMANE SELECT
NM_001127510.3:c.7663T>C
NM_001127511.3:c.7609T>C
NM_001354895.2:c.7663T>C
NM_001354896.2:c.7717T>C
NM_001354897.2:c.7693T>C
NM_001354898.2:c.7588T>C
NM_001354899.2:c.7579T>C
NM_001354900.2:c.7540T>C
NM_001354901.2:c.7486T>C
NM_001354902.2:c.7390T>C
NM_001354903.2:c.7360T>C
NM_001354904.2:c.7285T>C
NM_001354905.2:c.7183T>C
NM_001354906.2:c.6814T>C
NP_000029.2:p.Ser2555Pro
NP_001120982.1:p.Ser2555Pro
NP_001120983.2:p.Ser2537Pro
NP_001341824.1:p.Ser2555Pro
NP_001341825.1:p.Ser2573Pro
NP_001341826.1:p.Ser2565Pro
NP_001341827.1:p.Ser2530Pro
NP_001341828.1:p.Ser2527Pro
NP_001341829.1:p.Ser2514Pro
NP_001341830.1:p.Ser2496Pro
NP_001341831.1:p.Ser2464Pro
NP_001341832.1:p.Ser2454Pro
NP_001341833.1:p.Ser2429Pro
NP_001341834.1:p.Ser2395Pro
NP_001341835.1:p.Ser2272Pro
LRG_130:g.155737T>C
NC_000005.9:g.112178954T>C

Protein change:

S2272P

Links:

dbSNP: rs370581125

NCBI 1000 Genomes Browser:

rs370581125

Molecular consequence:

NM_000038.6:c.7663T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001127510.3:c.7663T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001127511.3:c.7609T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354895.2:c.7663T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354896.2:c.7717T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354897.2:c.7693T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354898.2:c.7588T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354899.2:c.7579T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354900.2:c.7540T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354901.2:c.7486T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354902.2:c.7390T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354903.2:c.7360T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354904.2:c.7285T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354905.2:c.7183T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354906.2:c.6814T>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

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002157251	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 26, 2022)	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

SCV002157251

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 26, 2022)

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV002157251.3

#	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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 1381848). 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 serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 2555 of the APC protein (p.Ser2555Pro).

#	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: Oct 26, 2024

ClinVar

Relating variation to medicine