NM_000251.3(MSH2):c.114C>G (p.Asp38Glu) AND not provided

Germline classification:: Likely benign (2 submissions)
Last evaluated:: Oct 18, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001564699.4

Allele description [Variation Report for NM_000251.3(MSH2):c.114C>G (p.Asp38Glu)]

NM_000251.3(MSH2):c.114C>G (p.Asp38Glu)

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.114C>G (p.Asp38Glu)

HGVS:

NC_000002.12:g.47403305C>G
NG_007110.2:g.5182C>G
NM_000251.3:c.114C>GMANE SELECT
NM_001258281.1:c.-30-55C>G
NP_000242.1:p.Asp38Glu
NP_000242.1:p.Asp38Glu
LRG_218t1:c.114C>G
LRG_218:g.5182C>G
LRG_218p1:p.Asp38Glu
NC_000002.11:g.47630444C>G
NM_000251.1:c.114C>G
NM_000251.2:c.114C>G
p.D38E

Protein change:

D38E

Links:

dbSNP: rs587779074

NCBI 1000 Genomes Browser:

rs587779074

Molecular consequence:

NM_001258281.1:c.-30-55C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000251.3:c.114C>G - missense variant - [Sequence Ontology: SO:0001583]

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
SCV001787899	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely benign (Mar 17, 2021)	germline	clinical testing	Citation Link,
SCV004220936	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Likely benign (Oct 18, 2022)	unknown	clinical testing	PubMed (5) [See all records that cite these PMIDs] 15849733, 15943554, 26333163, 18446350, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001787899

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely benign
(Mar 17, 2021)

germline

clinical testing

Citation Link,

SCV004220936

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Likely benign
(Oct 18, 2022)

unknown

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

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	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Spectrum and frequencies of mutations in MSH2 and MLH1 identified in 1,721 German families suspected of hereditary nonpolyposis colorectal cancer.

Mangold E, Pagenstecher C, Friedl W, Mathiak M, Buettner R, Engel C, Loeffler M, Holinski-Feder E, Müller-Koch Y, Keller G, Schackert HK, Krüger S, Goecke T, Moeslein G, Kloor M, Gebert J, Kunstmann E, Schulmann K, Rüschoff J, Propping P.

Int J Cancer. 2005 Sep 20;116(5):692-702.

PubMed [citation]

PMID:: 15849733

Deletions account for 17% of pathogenic germline alterations in MLH1 and MSH2 in hereditary nonpolyposis colorectal cancer (HNPCC) families.

Grabowski M, Mueller-Koch Y, Grasbon-Frodl E, Koehler U, Keller G, Vogelsang H, Dietmaier W, Kopp R, Siebers U, Schmitt W, Neitzel B, Gruber M, Doerner C, Kerker B, Ruemmele P, Henke G, Holinski-Feder E.

Genet Test. 2005 Summer;9(2):138-46.

PubMed [citation]

PMID:: 15943554

See all PubMed Citations (5)

Details of each submission

From GeneDx, SCV001787899.1

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

Description

In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in individuals with colorectal cancer or suspected Lynch syndrome, and co-occurred with an in-frame MSH2 deletion (phase unknown) in two siblings with normal tumor immunohistochemistry (Grabowski 2005, Mangold 2005, Urso 2008, Yurgelun 2015); This variant is associated with the following publications: (PMID: 31428572, 18446350, 25980754, 15849733, 26333163, 15943554)

#	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

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV004220936.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

#	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		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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