NM_000038.6(APC):c.385G>C (p.Glu129Gln) AND not provided

Clinical significance:Likely benign (Last evaluated: Dec 13, 2019)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
5 submissions [Details]
Record status:
current
Accession:
RCV000589545.5

Allele description [Variation Report for NM_000038.6(APC):c.385G>C (p.Glu129Gln)]

NM_000038.6(APC):c.385G>C (p.Glu129Gln)

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.385G>C (p.Glu129Gln)
HGVS:
  • NC_000005.10:g.112767353G>C
  • NG_008481.4:g.79833G>C
  • NM_000038.6:c.385G>CMANE SELECT
  • NM_001127510.3:c.385G>C
  • NM_001127511.3:c.415G>C
  • NM_001354895.2:c.385G>C
  • NM_001354896.2:c.385G>C
  • NM_001354897.2:c.415G>C
  • NM_001354898.2:c.310G>C
  • NM_001354899.2:c.385G>C
  • NM_001354900.2:c.208G>C
  • NM_001354901.2:c.208G>C
  • NM_001354902.2:c.415G>C
  • NM_001354903.2:c.385G>C
  • NM_001354904.2:c.310G>C
  • NM_001354905.2:c.208G>C
  • NM_001354906.2:c.-651G>C
  • NP_000029.2:p.Glu129Gln
  • NP_001120982.1:p.Glu129Gln
  • NP_001120983.2:p.Glu139Gln
  • NP_001341824.1:p.Glu129Gln
  • NP_001341825.1:p.Glu129Gln
  • NP_001341826.1:p.Glu139Gln
  • NP_001341827.1:p.Glu104Gln
  • NP_001341828.1:p.Glu129Gln
  • NP_001341829.1:p.Glu70Gln
  • NP_001341830.1:p.Glu70Gln
  • NP_001341831.1:p.Glu139Gln
  • NP_001341832.1:p.Glu129Gln
  • NP_001341833.1:p.Glu104Gln
  • NP_001341834.1:p.Glu70Gln
  • LRG_130:g.79833G>C
  • NC_000005.9:g.112103050G>C
  • NM_000038.5:c.385G>C
Protein change:
E104Q
Links:
dbSNP: rs376628500
NCBI 1000 Genomes Browser:
rs376628500
Molecular consequence:
  • NM_001354906.2:c.-651G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_000038.6:c.385G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127510.3:c.385G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127511.3:c.415G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354895.2:c.385G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354896.2:c.385G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354897.2:c.415G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354898.2:c.310G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354899.2:c.385G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354900.2:c.208G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354901.2:c.208G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354902.2:c.415G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354903.2:c.385G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354904.2:c.310G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354905.2:c.208G>C - 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
SCV000490404GeneDxcriteria provided, single submitter
Likely benign
(May 29, 2019)
germlineclinical testing

Citation Link,

SCV000694039Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Likely benign
(May 9, 2016)
germlineclinical testing

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

LabCorp Variant Classification Summary - May 2015.docx,

Citation Link,

SCV001470644Quest Diagnostics Nichols Institute San Juan Capistranocriteria provided, single submitter
Likely benign
(Dec 13, 2019)
unknownclinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV001799446Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) - VKGL Data-share Consensusno assertion criteria providedLikely benigngermlineclinical testing

SCV001922571Clinical Genetics,Academic Medical Center - VKGL Data-share Consensus

See additional submitters

no assertion criteria providedLikely benigngermlineclinical testing

Summary from all submissions

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

Citations

PubMed

Secondary resistance to immunotherapy associated with β-catenin pathway activation or PTEN loss in metastatic melanoma.

Trujillo JA, Luke JJ, Zha Y, Segal JP, Ritterhouse LL, Spranger S, Matijevich K, Gajewski TF.

J Immunother Cancer. 2019 Nov 8;7(1):295. doi: 10.1186/s40425-019-0780-0.

PubMed [citation]
PMID:
31703593
PMCID:
PMC6839232

Germline variation in cancer-susceptibility genes in a healthy, ancestrally diverse cohort: implications for individual genome sequencing.

Bodian DL, McCutcheon JN, Kothiyal P, Huddleston KC, Iyer RK, Vockley JG, Niederhuber JE.

PLoS One. 2014;9(4):e94554. doi: 10.1371/journal.pone.0094554.

PubMed [citation]
PMID:
24728327
PMCID:
PMC3984285
See all PubMed Citations (3)

Details of each submission

From GeneDx, SCV000490404.2

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

Description

This variant is associated with the following publications: (PMID: 24728327, 28615371, 29753010, 30093976)

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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000694039.1

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

Description

Variant summary: The APC c.385G>C (p.Glu129Gln) variant involves the alteration of a conserved nucleotide. 2/4 in silico tools predict a benign outcome (SNPs&GO not captured due to low reliability index). This variant was found in 8/122738 control chromosomes, predominantly observed in the East Asian subpopulation at a frequency of 0.000911 (8/8772). This frequency is about 15 times the estimated maximal expected allele frequency of a pathogenic APC variant (0.0000602), suggesting this is likely a benign polymorphism found primarily in populations of East Asian origin. A clinical diagnostic laboratory classified this variant as Uncertain. The variant of interest has not, to our knowledge, been reported in affected individuals via publications; nor evaluated for functional impact by in vivo/vitro studies. Considering the high prevalence of the variant in the East ASian population, it was classified as Likely Benign.

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

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV001470644.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) - VKGL Data-share Consensus, SCV001799446.1

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

From Clinical Genetics,Academic Medical Center - VKGL Data-share Consensus, SCV001922571.1

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

Last Updated: Nov 27, 2021

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