NM_000038.6(APC):c.317G>A (p.Arg106His) AND Classic or attenuated familial adenomatous polyposis

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 11, 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:: RCV003996161.2

Allele description [Variation Report for NM_000038.6(APC):c.317G>A (p.Arg106His)]

NM_000038.6(APC):c.317G>A (p.Arg106His)

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.317G>A (p.Arg106His)

HGVS:

NC_000005.10:g.112767285G>A
NG_008481.4:g.79765G>A
NM_000038.6:c.317G>AMANE SELECT
NM_001127510.3:c.317G>A
NM_001127511.3:c.347G>A
NM_001354895.2:c.317G>A
NM_001354896.2:c.317G>A
NM_001354897.2:c.347G>A
NM_001354898.2:c.242G>A
NM_001354899.2:c.317G>A
NM_001354900.2:c.140G>A
NM_001354901.2:c.140G>A
NM_001354902.2:c.347G>A
NM_001354903.2:c.317G>A
NM_001354904.2:c.242G>A
NM_001354905.2:c.140G>A
NM_001354906.2:c.-719G>A
NP_000029.2:p.Arg106His
NP_001120982.1:p.Arg106His
NP_001120983.2:p.Arg116His
NP_001341824.1:p.Arg106His
NP_001341825.1:p.Arg106His
NP_001341826.1:p.Arg116His
NP_001341827.1:p.Arg81His
NP_001341828.1:p.Arg106His
NP_001341829.1:p.Arg47His
NP_001341830.1:p.Arg47His
NP_001341831.1:p.Arg116His
NP_001341832.1:p.Arg106His
NP_001341833.1:p.Arg81His
NP_001341834.1:p.Arg47His
LRG_130t1:c.317G>A
LRG_130:g.79765G>A
NC_000005.9:g.112102982G>A
NM_000038.4:c.317G>A
NM_000038.5:c.317G>A

Protein change:

R106H

Links:

dbSNP: rs201764637

NCBI 1000 Genomes Browser:

rs201764637

Molecular consequence:

NM_001354906.2:c.-719G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000038.6:c.317G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001127510.3:c.317G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001127511.3:c.347G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354895.2:c.317G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354896.2:c.317G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354897.2:c.347G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354898.2:c.242G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354899.2:c.317G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354900.2:c.140G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354901.2:c.140G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354902.2:c.347G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354903.2:c.317G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354904.2:c.242G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354905.2:c.140G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Classic or attenuated familial adenomatous polyposis
Identifiers:: MONDO: MONDO:0021057; MedGen: CN372698

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004837255	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain Significance (Jan 11, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 18199528, 21859464, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004837255

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain Significance
(Jan 11, 2024)

germline

clinical testing

PubMed (3)
[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	6	not provided	not provided	108544	not provided	clinical testing

Citations

PubMed

Multiple rare nonsynonymous variants in the adenomatous polyposis coli gene predispose to colorectal adenomas.

Azzopardi D, Dallosso AR, Eliason K, Hendrickson BC, Jones N, Rawstorne E, Colley J, Moskvina V, Frye C, Sampson JR, Wenstrup R, Scholl T, Cheadle JP.

Cancer Res. 2008 Jan 15;68(2):358-63. doi: 10.1158/0008-5472.CAN-07-5733.

PubMed [citation]

PMID:: 18199528

Messing up disorder: how do missense mutations in the tumor suppressor protein APC lead to cancer?

Minde DP, Anvarian Z, Rüdiger SG, Maurice MM.

Mol Cancer. 2011 Aug 22;10:101. doi: 10.1186/1476-4598-10-101. Review.

PubMed [citation]

PMID:: 21859464
PMCID:: PMC3170638

See all PubMed Citations (3)

Details of each submission

From All of Us Research Program, National Institutes of Health, SCV004837255.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	6	not provided	not provided	clinical testing	PubMed (3)

Description

This missense variant replaces arginine with histidine at codon 106 of the APC protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with adenomatous polyposis (PMID: 18199528, 21859464). This variant has also been identified in 13/282866 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is 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	108544	not provided	not provided		6	not provided	not provided	not provided

Last Updated: Oct 8, 2024

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