NM_000251.3(MSH2):c.1270C>T (p.His424Tyr) AND not provided

Clinical significance:Uncertain significance (Last evaluated: May 23, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000481281.2

Allele description [Variation Report for NM_000251.3(MSH2):c.1270C>T (p.His424Tyr)]

NM_000251.3(MSH2):c.1270C>T (p.His424Tyr)

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.1270C>T (p.His424Tyr)
HGVS:
  • NC_000002.12:g.47429935C>T
  • NG_007110.2:g.31812C>T
  • NM_000251.3:c.1270C>TMANE SELECT
  • NM_001258281.1:c.1072C>T
  • NP_000242.1:p.His424Tyr
  • NP_000242.1:p.His424Tyr
  • NP_001245210.1:p.His358Tyr
  • LRG_218t1:c.1270C>T
  • LRG_218:g.31812C>T
  • LRG_218p1:p.His424Tyr
  • NC_000002.11:g.47657074C>T
  • NM_000251.1:c.1270C>T
  • NM_000251.2:c.1270C>T
  • p.H424Y
Protein change:
H358Y
Links:
dbSNP: rs587782278
NCBI 1000 Genomes Browser:
rs587782278
Molecular consequence:
  • NM_000251.3:c.1270C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001258281.1:c.1072C>T - 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
SCV000565728GeneDxcriteria provided, single submitter
Uncertain significance
(May 23, 2018)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From GeneDx, SCV000565728.4

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

Description

This variant is denoted MSH2 c.1270C>T at the cDNA level, p.His424Tyr (H424Y) at the protein level, and results in the change of a Histidine to a Tyrosine (CAT>TAT). This variant was observed in at least one individual with ovarian cancer as well as at least one control (Pal 2012, DeRycke 2017). MSH2 His424Tyr was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the Lever domain and the region of interaction with MSH6 and MSH3 (Guerrette 1998, 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 His424Tyr 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

Last Updated: Dec 4, 2021

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