NM_000038.6(APC):c.7128G>C (p.Gln2376His) AND Familial adenomatous polyposis 1

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Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 4, 2024
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:: RCV003534521.1

Allele description

NM_000038.6(APC):c.7128G>C (p.Gln2376His)

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.7128G>C (p.Gln2376His)

HGVS:

NC_000005.10:g.112842722G>C
NG_008481.4:g.155202G>C
NM_000038.6:c.7128G>CMANE SELECT
NM_001127510.3:c.7128G>C
NM_001127511.3:c.7074G>C
NM_001354895.2:c.7128G>C
NM_001354896.2:c.7182G>C
NM_001354897.2:c.7158G>C
NM_001354898.2:c.7053G>C
NM_001354899.2:c.7044G>C
NM_001354900.2:c.7005G>C
NM_001354901.2:c.6951G>C
NM_001354902.2:c.6855G>C
NM_001354903.2:c.6825G>C
NM_001354904.2:c.6750G>C
NM_001354905.2:c.6648G>C
NM_001354906.2:c.6279G>C
NP_000029.2:p.Gln2376His
NP_001120982.1:p.Gln2376His
NP_001120983.2:p.Gln2358His
NP_001341824.1:p.Gln2376His
NP_001341825.1:p.Gln2394His
NP_001341826.1:p.Gln2386His
NP_001341827.1:p.Gln2351His
NP_001341828.1:p.Gln2348His
NP_001341829.1:p.Gln2335His
NP_001341830.1:p.Gln2317His
NP_001341831.1:p.Gln2285His
NP_001341832.1:p.Gln2275His
NP_001341833.1:p.Gln2250His
NP_001341834.1:p.Gln2216His
NP_001341835.1:p.Gln2093His
LRG_130:g.155202G>C
NC_000005.9:g.112178419G>C
NM_000038.5:c.7128G>C

Protein change:

Q2093H

Links:

dbSNP: rs762167924

NCBI 1000 Genomes Browser:

rs762167924

Molecular consequence:

NM_000038.6:c.7128G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001127510.3:c.7128G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001127511.3:c.7074G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354895.2:c.7128G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354896.2:c.7182G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354897.2:c.7158G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354898.2:c.7053G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354899.2:c.7044G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354900.2:c.7005G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354901.2:c.6951G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354902.2:c.6855G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354903.2:c.6825G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354904.2:c.6750G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354905.2:c.6648G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354906.2:c.6279G>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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Mus musculus cDNA clone IMAGE:9053268
Mus musculus cDNA clone IMAGE:9053268
gi|219519711|gb|BC144720.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000812909	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 4, 2024)	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

SCV000812909

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 4, 2024)

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, SCV000812909.7

#	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 glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 2376 of the APC protein (p.Gln2376His). This variant is present in population databases (rs762167924, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 231537). 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 with a negative predictive value of 95%. 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 2, 2024

ClinVar

Relating variation to medicine