NM_000038.6(APC):c.995G>A (p.Arg332Gln) AND Familial adenomatous polyposis 1

Clinical significance:Uncertain significance (Last evaluated: Oct 29, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000200721.6

Allele description [Variation Report for NM_000038.6(APC):c.995G>A (p.Arg332Gln)]

NM_000038.6(APC):c.995G>A (p.Arg332Gln)

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.995G>A (p.Arg332Gln)
HGVS:
  • NC_000005.10:g.112819027G>A
  • NG_008481.4:g.131507G>A
  • NM_000038.6:c.995G>AMANE SELECT
  • NM_001127510.3:c.995G>A
  • NM_001127511.3:c.941G>A
  • NM_001354895.2:c.995G>A
  • NM_001354896.2:c.995G>A
  • NM_001354897.2:c.1025G>A
  • NM_001354898.2:c.920G>A
  • NM_001354899.2:c.911G>A
  • NM_001354900.2:c.818G>A
  • NM_001354901.2:c.818G>A
  • NM_001354902.2:c.964-242G>A
  • NM_001354903.2:c.934-242G>A
  • NM_001354904.2:c.859-242G>A
  • NM_001354905.2:c.757-242G>A
  • NM_001354906.2:c.146G>A
  • NP_000029.2:p.Arg332Gln
  • NP_001120982.1:p.Arg332Gln
  • NP_001120983.2:p.Arg314Gln
  • NP_001341824.1:p.Arg332Gln
  • NP_001341825.1:p.Arg332Gln
  • NP_001341826.1:p.Arg342Gln
  • NP_001341827.1:p.Arg307Gln
  • NP_001341828.1:p.Arg304Gln
  • NP_001341829.1:p.Arg273Gln
  • NP_001341830.1:p.Arg273Gln
  • NP_001341835.1:p.Arg49Gln
  • LRG_130:g.131507G>A
  • NC_000005.9:g.112154724G>A
  • NM_000038.5:c.995G>A
  • p.R332Q
Protein change:
R273Q
Links:
dbSNP: rs377665107
NCBI 1000 Genomes Browser:
rs377665107
Molecular consequence:
  • NM_001354902.2:c.964-242G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001354903.2:c.934-242G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001354904.2:c.859-242G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001354905.2:c.757-242G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000038.6:c.995G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127510.3:c.995G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127511.3:c.941G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354895.2:c.995G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354896.2:c.995G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354897.2:c.1025G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354898.2:c.920G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354899.2:c.911G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354900.2:c.818G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354901.2:c.818G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354906.2:c.146G>A - 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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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000254053Invitaecriteria provided, single submitter
Uncertain significance
(Oct 29, 2020)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV000785636Counsylcriteria provided, single submitter
Uncertain significance
(Oct 17, 2017)
unknownclinical testing

Counsyl_Autosomal_Dominant_Disease_Classification_criteria_(2015)_v1.pdf

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000254053.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change replaces arginine with glutamine at codon 332 of the APC protein (p.Arg332Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs377665107, ExAC 0.01%). This variant has not been reported in the literature in individuals with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 187754). 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Counsyl, SCV000785636.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jun 19, 2021

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