NM_000251.3(MSH2):c.20del (p.Glu7fs) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Oct 27, 2017
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:: RCV000202031.5

Allele description [Variation Report for NM_000251.3(MSH2):c.20del (p.Glu7fs)]

NM_000251.3(MSH2):c.20del (p.Glu7fs)

Gene:

MSH2:mutS homolog 2 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

2p21

Genomic location:

Preferred name:

NM_000251.3(MSH2):c.20del (p.Glu7fs)

HGVS:

NC_000002.12:g.47403211del
NG_007110.2:g.5088del
NM_000251.3:c.20delMANE SELECT
NM_001258281.1:c.-31+36del
NP_000242.1:p.Glu7fs
NP_000242.1:p.Glu7fs
LRG_218t1:c.20del
LRG_218:g.5088del
LRG_218p1:p.Glu7fs
NC_000002.11:g.47630350del
NM_000251.1:c.20del
NM_000251.1:c.20delA
NM_000251.2:c.20del
NM_000251.2:c.20delA

Protein change:

E7fs

Links:

dbSNP: rs267607915

NCBI 1000 Genomes Browser:

rs267607915

Molecular consequence:

NM_000251.3:c.20del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001258281.1:c.-31+36del - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000257167	Mayo Clinic Laboratories, Mayo Clinic	no assertion criteria provided	Likely pathogenic	unknown	research
SCV000778970	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Oct 27, 2017)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000257167

Mayo Clinic Laboratories, Mayo Clinic

no assertion criteria provided

Likely pathogenic

unknown

research

SCV000778970

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Oct 27, 2017)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	1	not provided	not provided	not provided	not provided	research

Details of each submission

From Mayo Clinic Laboratories, Mayo Clinic, SCV000257167.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	research	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		1	not provided	not provided	not provided

From GeneDx, SCV000778970.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

This deletion of one nucleotide in MSH2 is denoted c.20delA at the cDNA level and p.Glu7GlyfsX57 (E7GfsX57) at the protein level. The normal sequence, with the base that is deleted in brackets, is AAGG[delA]GACG. The deletion causes a frameshift which changes a Glutamic Acid to a Glycine at codon 7, and creates a premature stop codon at position 57 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. MSH2 c.20delA has been observed in at least one family suspected of having Lynch syndrome; and in another individual with a personal history of colorectal cancer, whose tumor studies demonstrated microsatellite instability and absence of MSH2 protein expression on immunohistochemistry (Julie 2008, Bonadona 2011). We consider this variant to be pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 1, 2024

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