NM_004655.4(AXIN2):c.2282C>A (p.Ala761Asp) AND not specified

Clinical significance:Benign/Likely benign (Last evaluated: Apr 6, 2018)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
4 submissions [Details]
Record status:
current
Accession:
RCV000212103.5

Allele description [Variation Report for NM_004655.4(AXIN2):c.2282C>A (p.Ala761Asp)]

NM_004655.4(AXIN2):c.2282C>A (p.Ala761Asp)

Gene:
AXIN2:axin 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17q24.1
Genomic location:
Preferred name:
NM_004655.4(AXIN2):c.2282C>A (p.Ala761Asp)
Other names:
p.A761D:GCC>GAC
HGVS:
  • NC_000017.11:g.65534035G>T
  • NG_012142.1:g.32588C>A
  • NM_001363813.1:c.2087C>A
  • NM_004655.4:c.2282C>AMANE SELECT
  • NP_001350742.1:p.Ala696Asp
  • NP_004646.3:p.Ala761Asp
  • LRG_296t1:c.2282C>A
  • LRG_296:g.32588C>A
  • NC_000017.10:g.63530153G>T
  • NM_004655.3:c.2282C>A
Protein change:
A696D
Links:
dbSNP: rs79732150
NCBI 1000 Genomes Browser:
rs79732150
Molecular consequence:
  • NM_001363813.1:c.2087C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004655.4:c.2282C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000167149GeneDxcriteria provided, single submitter
Benign
(Oct 11, 2013)
germlineclinical testing

Citation Link,

SCV000593564Genetic Services Laboratory,University of Chicagocriteria provided, single submitter
Likely benign
(Aug 19, 2016)
germlineclinical testing

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

SCV000691771Mayo Clinic Laboratories, Mayo Clinicno assertion criteria providedBenignunknownclinical testing

SCV000916642Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Benign
(Apr 6, 2018)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlinenonot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From GeneDx, SCV000167149.11

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

Description

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

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

From Genetic Services Laboratory,University of Chicago, SCV000593564.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenonot providednot providednot providednot providednot providednot providednot provided

From Mayo Clinic Laboratories, Mayo Clinic, SCV000691771.1

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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000916642.1

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

Description

Variant summary: AXIN2 c.2282C>A (p.Ala761Asp) results in a non-conservative amino acid change located in the DIX domain of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0018 in 121402 control chromosomes. The observed variant frequency is approximately 13 fold of the estimated maximal expected allele frequency for a pathogenic variant in AXIN2 causing Colorectal Cancer phenotype (0.00014), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.2282C>A in individuals affected with Colorectal Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.

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

Last Updated: Oct 30, 2021

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