NM_000251.3(MSH2):c.1489A>G (p.Ile497Val) AND not provided

Clinical significance:Uncertain significance (Last evaluated: Nov 2, 2018)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000483517.2

Allele description [Variation Report for NM_000251.3(MSH2):c.1489A>G (p.Ile497Val)]

NM_000251.3(MSH2):c.1489A>G (p.Ile497Val)

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.1489A>G (p.Ile497Val)
HGVS:
  • NC_000002.12:g.47463133A>G
  • NG_007110.2:g.65010A>G
  • NM_000251.2:c.1489A>G
  • NM_000251.3:c.1489A>GMANE SELECT
  • NM_001258281.1:c.1291A>G
  • NP_000242.1:p.Ile497Val
  • NP_000242.1:p.Ile497Val
  • NP_001245210.1:p.Ile431Val
  • LRG_218t1:c.1489A>G
  • LRG_218:g.65010A>G
  • LRG_218p1:p.Ile497Val
  • NC_000002.11:g.47690272A>G
  • NM_000251.1:c.1489A>G
Protein change:
I431V
Links:
dbSNP: rs755501968
NCBI 1000 Genomes Browser:
rs755501968
Molecular consequence:
  • NM_000251.2:c.1489A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000251.3:c.1489A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001258281.1:c.1291A>G - 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
SCV000567758GeneDxcriteria provided, single submitter
Uncertain significance
(Apr 6, 2018)
germlineclinical testing

Citation Link,

SCV001134339Quest Diagnostics Nichols Institute San Juan Capistranocriteria provided, single submitter
Uncertain significance
(Nov 2, 2018)
germlineclinical testing

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

Summary from all submissions

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

Citations

PubMed

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]
PMID:
26467025
PMCID:
PMC4737317

Details of each submission

From GeneDx, SCV000567758.5

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

Description

This variant is denoted MSH2 c.1489A>G at the cDNA level, p.Ile497Val (I497V) at the protein level, and results in the change of an Isoleucine to a Valine (ATA>GTA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. MSH2 Ile497Val was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the Clamp domain and the region of interaction with MSH6 and MSH3 (Guerrette 1998, L?tzen 2008, Kansikas 2011). While protein-based in silico analyses predict that this variant is unlikely to alter protein structure or function, multiple splicing models predict that this variant may create a cryptic splice donor site upstream of the natural splice donor, leading to abnormal splicing. However, in the absence of RNA or functional studies, the actual effect of this variant is unknown. Based on currently available evidence, it is unclear whether MSH2 Ile497Val 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

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV001134339.1

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

Last Updated: Oct 30, 2021

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