NM_000038.6(APC):c.7771C>G (p.His2591Asp) AND Familial adenomatous polyposis 1

delete

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 28, 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:: RCV003651933.1

Allele description

NM_000038.6(APC):c.7771C>G (p.His2591Asp)

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.7771C>G (p.His2591Asp)

HGVS:

NC_000005.10:g.112843365C>G
NG_008481.4:g.155845C>G
NM_000038.6:c.7771C>GMANE SELECT
NM_001127510.3:c.7771C>G
NM_001127511.3:c.7717C>G
NM_001354895.2:c.7771C>G
NM_001354896.2:c.7825C>G
NM_001354897.2:c.7801C>G
NM_001354898.2:c.7696C>G
NM_001354899.2:c.7687C>G
NM_001354900.2:c.7648C>G
NM_001354901.2:c.7594C>G
NM_001354902.2:c.7498C>G
NM_001354903.2:c.7468C>G
NM_001354904.2:c.7393C>G
NM_001354905.2:c.7291C>G
NM_001354906.2:c.6922C>G
NP_000029.2:p.His2591Asp
NP_001120982.1:p.His2591Asp
NP_001120983.2:p.His2573Asp
NP_001341824.1:p.His2591Asp
NP_001341825.1:p.His2609Asp
NP_001341826.1:p.His2601Asp
NP_001341827.1:p.His2566Asp
NP_001341828.1:p.His2563Asp
NP_001341829.1:p.His2550Asp
NP_001341830.1:p.His2532Asp
NP_001341831.1:p.His2500Asp
NP_001341832.1:p.His2490Asp
NP_001341833.1:p.His2465Asp
NP_001341834.1:p.His2431Asp
NP_001341835.1:p.His2308Asp
LRG_130:g.155845C>G
NC_000005.9:g.112179062C>G
NM_000038.5:c.7771C>G

Protein change:

H2308D

Links:

dbSNP: rs1114167572

NCBI 1000 Genomes Browser:

rs1114167572

Molecular consequence:

NM_000038.6:c.7771C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001127510.3:c.7771C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001127511.3:c.7717C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354895.2:c.7771C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354896.2:c.7825C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354897.2:c.7801C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354898.2:c.7696C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354899.2:c.7687C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354900.2:c.7648C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354901.2:c.7594C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354902.2:c.7498C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354903.2:c.7468C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354904.2:c.7393C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354905.2:c.7291C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354906.2:c.6922C>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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004502077	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 28, 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

SCV004502077

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 28, 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, SCV004502077.1

#	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 histidine, which is basic and polar, with aspartic acid, which is acidic and polar, at codon 2591 of the APC protein (p.His2591Asp). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with APC-related conditions. 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. ClinVar contains an entry for this variant (Variation ID: 428129). 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: May 1, 2024

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