NM_000251.2(MSH2):c.2680dup (p.Met894fs) AND not provided

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Aug 22, 2017)

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:
RCV000657245.2

Allele description [Variation Report for NM_000251.2(MSH2):c.2680dup (p.Met894fs)]

NM_000251.2(MSH2):c.2680dup (p.Met894fs)

Gene:
MSH2:mutS homolog 2 [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
2p21
Genomic location:
Preferred name:
NM_000251.2(MSH2):c.2680dup (p.Met894fs)
Other names:
p.Met894AsnfsX5
HGVS:
  • NC_000002.11:g.47709960_47709961insA
  • NC_000002.12:g.47482824dup
  • NG_007110.2:g.84701dup
  • NM_000251.3:c.2680dupMANE SELECT
  • NM_001258281.1:c.2482dup
  • NP_001245210.1:p.Met828fs
  • LRG_218t1:c.2680dup
  • LRG_218:g.84701dup
  • LRG_218p1:p.Met894fs
  • NC_000002.11:g.47709960_47709961insA
  • NC_000002.11:g.47709963_47709964insA
  • NC_000002.11:g.47709963dup
  • NM_000251.1:c.2680dupA
  • NM_000251.2:c.2680dupA
Protein change:
M828fs
Links:
dbSNP: rs876658211
NCBI 1000 Genomes Browser:
rs876658211
Molecular consequence:
  • NM_001258281.1:c.2482dup - frameshift variant - [Sequence Ontology: SO:0001589]
Observations:
6

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000778975GeneDxcriteria provided, single submitter
Likely pathogenic
(Aug 22, 2017)
germlineclinical testing

Citation Link,

SCV001449568Clinical Genetics Karolinska University Hospital,Karolinska University Hospitalcriteria provided, single submitter
Pathogenic
(Sep 10, 2014)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes6not providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From GeneDx, SCV000778975.2

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

Description

This duplication of one nucleotide in MSH2 is denoted c.2680dupA at the cDNA level and p.Met894AsnfsX5 (M894NfsX5) at the protein level. The normal sequence, with the base that is duplicated in brackets, is ACAA[dupA]TGCC. The duplication causes a frameshift which changes a Methionine to an Asparagine at codon 894, and creates a premature stop codon at position 5 of the new reading frame. This variant is predicted to cause loss of normal protein function through protein truncation. MSH2 c.2680dupA has been reported in individuals with Lynch syndrome, and mismatch repair immunohistochemistry (MMR IHC) data available on a tumor showed loss of MSH2 and MSH6 in at least one carrier (Casey 2005, Lagerstedt-Robinson 2016). Based on the currently available information, we consider this duplication to be a likely pathogenic variant.

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

From Clinical Genetics Karolinska University Hospital,Karolinska University Hospital, SCV001449568.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided6not providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided6not providednot providednot provided

Last Updated: Jul 7, 2021

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