NM_000038.6(APC):c.7780T>C (p.Ser2594Pro) AND Familial adenomatous polyposis 1

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 25, 2021
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:: RCV003773166.2

Allele description [Variation Report for NM_000038.6(APC):c.7780T>C (p.Ser2594Pro)]

NM_000038.6(APC):c.7780T>C (p.Ser2594Pro)

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.7780T>C (p.Ser2594Pro)

HGVS:

NC_000005.10:g.112843374T>C
NG_008481.4:g.155854T>C
NM_000038.6:c.7780T>CMANE SELECT
NM_001127510.3:c.7780T>C
NM_001127511.3:c.7726T>C
NM_001354895.2:c.7780T>C
NM_001354896.2:c.7834T>C
NM_001354897.2:c.7810T>C
NM_001354898.2:c.7705T>C
NM_001354899.2:c.7696T>C
NM_001354900.2:c.7657T>C
NM_001354901.2:c.7603T>C
NM_001354902.2:c.7507T>C
NM_001354903.2:c.7477T>C
NM_001354904.2:c.7402T>C
NM_001354905.2:c.7300T>C
NM_001354906.2:c.6931T>C
NP_000029.2:p.Ser2594Pro
NP_001120982.1:p.Ser2594Pro
NP_001120983.2:p.Ser2576Pro
NP_001341824.1:p.Ser2594Pro
NP_001341825.1:p.Ser2612Pro
NP_001341826.1:p.Ser2604Pro
NP_001341827.1:p.Ser2569Pro
NP_001341828.1:p.Ser2566Pro
NP_001341829.1:p.Ser2553Pro
NP_001341830.1:p.Ser2535Pro
NP_001341831.1:p.Ser2503Pro
NP_001341832.1:p.Ser2493Pro
NP_001341833.1:p.Ser2468Pro
NP_001341834.1:p.Ser2434Pro
NP_001341835.1:p.Ser2311Pro
LRG_130:g.155854T>C
NC_000005.9:g.112179071T>C

Protein change:

S2311P

Links:

dbSNP: rs2149993690

NCBI 1000 Genomes Browser:

rs2149993690

Molecular consequence:

NM_000038.6:c.7780T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001127510.3:c.7780T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001127511.3:c.7726T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354895.2:c.7780T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354896.2:c.7834T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354897.2:c.7810T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354898.2:c.7705T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354899.2:c.7696T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354900.2:c.7657T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354901.2:c.7603T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354902.2:c.7507T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354903.2:c.7477T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354904.2:c.7402T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354905.2:c.7300T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354906.2:c.6931T>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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002276770	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 25, 2021)	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

SCV002276770

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 25, 2021)

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, SCV002276770.3

#	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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with proline at codon 2594 of the APC protein (p.Ser2594Pro). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and proline.

#	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: Nov 3, 2024

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