NM_000038.6(APC):c.995G>A (p.Arg332Gln) AND not provided

Clinical significance:Uncertain significance (Last evaluated: Aug 24, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000480823.2

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)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000569143GeneDxcriteria provided, single submitter
Uncertain significance
(Aug 24, 2017)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From GeneDx, SCV000569143.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

This variant is denoted APC c.995G>A at the cDNA level, p.Arg332Gln (R332Q) at the protein level, and results in the change of an Arginine to a Glutamine (CGA>CAA). This variant has not, to our knowledge, been published in the literature as pathogenic germline variant or a benign polymorphism. However, it has been reported as a somatic variant in a colorectal tumor that also harbored a truncating APC variant (Jesinghaus 2016). APC Arg332Gln was observed at an allele frequency of 0.012% (1/8628) in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Arginine and Glutamine differ in some properties, this is considered a semi-conservative amino acid substitution. APC Arg332Gln occurs at a position that is conserved across species and is not located in a known functional domain. In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, it is unclear whether APC Arg332Gln is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.

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

Last Updated: Jun 19, 2021

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