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NM_001048174.2(MUTYH):c.32G>A (p.Gly11Asp) AND Carcinoma of colon

Germline classification:
Uncertain significance (1 submission)
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV001353637.10

Allele description [Variation Report for NM_001048174.2(MUTYH):c.32G>A (p.Gly11Asp)]

NM_001048174.2(MUTYH):c.32G>A (p.Gly11Asp)

Gene:
MUTYH:mutY DNA glycosylase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1p34.1
Genomic location:
Preferred name:
NM_001048174.2(MUTYH):c.32G>A (p.Gly11Asp)
Other names:
p.G25D:GGT>GAT
HGVS:
  • NC_000001.11:g.45334474C>T
  • NG_008189.1:g.10997G>A
  • NM_001048171.2:c.32G>A
  • NM_001048172.2:c.32G>A
  • NM_001048173.2:c.32G>A
  • NM_001048174.2:c.32G>AMANE SELECT
  • NM_001128425.2:c.74G>A
  • NM_001293190.2:c.74G>A
  • NM_001293191.2:c.32G>A
  • NM_001293192.2:c.-181G>A
  • NM_001293195.2:c.32G>A
  • NM_001293196.2:c.-181G>A
  • NM_001350650.2:c.-240G>A
  • NM_001350651.2:c.-176G>A
  • NM_012222.3:c.74G>A
  • NP_001041636.1:p.Gly25Asp
  • NP_001041636.2:p.Gly11Asp
  • NP_001041637.1:p.Gly11Asp
  • NP_001041638.1:p.Gly11Asp
  • NP_001041639.1:p.Gly11Asp
  • NP_001121897.1:p.Gly25Asp
  • NP_001121897.1:p.Gly25Asp
  • NP_001280119.1:p.Gly25Asp
  • NP_001280120.1:p.Gly11Asp
  • NP_001280124.1:p.Gly11Asp
  • NP_036354.1:p.Gly25Asp
  • NP_036354.1:p.Gly25Asp
  • LRG_220t1:c.74G>A
  • LRG_220:g.10997G>A
  • LRG_220p1:p.Gly25Asp
  • NC_000001.10:g.45800146C>T
  • NM_001048171.1:c.74G>A
  • NM_001128425.1:c.74G>A
  • NM_012222.2:c.74G>A
  • NR_146882.2:n.260G>A
  • NR_146883.2:n.183G>A
  • p.G25D
Protein change:
G11D
Links:
dbSNP: rs75321043
NCBI 1000 Genomes Browser:
rs75321043
Molecular consequence:
  • NM_001293192.2:c.-181G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001293196.2:c.-181G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001350650.2:c.-240G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001350651.2:c.-176G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001048171.2:c.32G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001048172.2:c.32G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001048173.2:c.32G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001048174.2:c.32G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001128425.2:c.74G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293190.2:c.74G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293191.2:c.32G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293195.2:c.32G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_012222.3:c.74G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_146882.2:n.260G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146883.2:n.183G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
Observations:
2

Condition(s)

Name:
Carcinoma of colon (CRC)
Synonyms:
Colonic carcinoma; Colon carcinoma
Identifiers:
MONDO: MONDO:0002032; MedGen: C0699790

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000592675Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR)

See additional submitters

no assertion criteria provided
Uncertain significanceunknownclinical testing

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownyes2not providednot providednot providednot providedclinical testing

Details of each submission

From Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV000592675.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedclinical testingnot provided

Description

The p.Gly25Asp variant was identified in the literature in 18 of 896 proband chromosomes (frequency: 0.020) from Asian individuals (Korean, Chinese, Japanese) with adenomatous polyposis or colorectal cancer, and was present in 6 of 944 control chromosomes (frequency: 0.006) (Chen 2008, Kim 2007, Yanaru-Fujisawa 2008, Zhang 2006). In all these studies, the variant was identified in co-occurrence on the same allele as another MUTYH variant, p.Pro18Leu. Two studies suggest that this haplotype variant allele (containing both p.Pro18Leu and p.Gly25Asp variants) increases the risk of gastric cancer, with significantly higher frequencies of the variant haplotype observed in affected cases than in healthy controls (Chen 2008, Zhang 2006). In addition, a functional study by Chen (2008) found that the haplotype variant allele had a partial effect on protein mitochondrial transport as compared to wild type MUTYH protein. This effect, however, was not found when each variant was tested individually, suggesting an additive effect of the combined variants on the mitochondrial targeting sequences domain of the MUTYH protein. The variant was also identified in dbSNP (ID: rs75321043) “With allele of Uncertain significance” with a minor allele frequency of 0.003 (1000 Genomes Project), in HGMD, and in the “InSiGHT Colon Cancer Database”. The p.Gly25 residue is not conserved in mammals and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein. However, this information is not predictive enough to rule out pathogenicity. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time. Therefore, this variant is classified as a variant of unknown significance (VUS).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownyesnot providednot providednot provided2not providednot providednot provided

Last Updated: Oct 20, 2024