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NM_000251.3(MSH2):c.2503A>G (p.Asn835Asp) AND not provided

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Nov 28, 2018
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV000520077.2

Allele description [Variation Report for NM_000251.3(MSH2):c.2503A>G (p.Asn835Asp)]

NM_000251.3(MSH2):c.2503A>G (p.Asn835Asp)

Gene:
MSH2:mutS homolog 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2p21
Genomic location:
Preferred name:
NM_000251.3(MSH2):c.2503A>G (p.Asn835Asp)
HGVS:
  • NC_000002.12:g.47480740A>G
  • NG_007110.2:g.82617A>G
  • NM_000251.3:c.2503A>GMANE SELECT
  • NM_001258281.1:c.2305A>G
  • NP_000242.1:p.Asn835Asp
  • NP_000242.1:p.Asn835Asp
  • NP_001245210.1:p.Asn769Asp
  • LRG_218t1:c.2503A>G
  • LRG_218:g.82617A>G
  • LRG_218p1:p.Asn835Asp
  • NC_000002.11:g.47707879A>G
  • NM_000251.1:c.2503A>G
  • NM_000251.2:c.2503A>G
  • p.N835D
Protein change:
N769D
Links:
dbSNP: rs41295296
NCBI 1000 Genomes Browser:
rs41295296
Molecular consequence:
  • NM_000251.3:c.2503A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001258281.1:c.2305A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000616787GeneDx
criteria provided, single submitter

(GeneDx Variant Classification (06012015))		Uncertain significance
(Nov 28, 2018) 		germlineclinical testing

Citation Link

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Summary from all submissions

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

Details of each submission

From GeneDx, SCV000616787.2

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

Description

This variant is denoted MSH2 c.2503A>G at the cDNA level, p.Asn835Asp (N835D) at the protein level, and results in the change of an Asparagine to an Aspartic Acid (AAT>GAT). This variant was observed in at least two individuals with microsatellite unstable tumors, one with colon cancer who also harbored a second MSH2 missense variant, and another with endometrial cancer (Samowitz 2001, Hampel 2006). On functional interrogation, MSH2 Asn835Asp demonstrated mismatch repair proficiency in mouse embryonic stem cells (Houlleberghs 2016). This variant was not observed at a significant allele frequency in large population cohorts (Lek 2016). MSH2 Asn835Asp is located in the ATPase domain (Lutzen 2008, Kansikas 2011). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether MSH2 Asn835Asp is pathogenic or benign. 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: Sep 29, 2024