NM_000251.3(MSH2):c.380A>G (p.Asn127Ser) AND Lynch syndrome 1

Germline classification:: Conflicting interpretations of pathogenicity (6 submissions)
Last evaluated:: Jul 7, 2023
Review status:: criteria provided, conflicting classifications

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:: RCV000144619.18

Allele description [Variation Report for NM_000251.3(MSH2):c.380A>G (p.Asn127Ser)]

NM_000251.3(MSH2):c.380A>G (p.Asn127Ser)

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.380A>G (p.Asn127Ser)

HGVS:

NC_000002.12:g.47410107A>G
NG_007110.2:g.11984A>G
NM_000251.3:c.380A>GMANE SELECT
NM_001258281.1:c.182A>G
NP_000242.1:p.Asn127Ser
NP_000242.1:p.Asn127Ser
NP_001245210.1:p.Asn61Ser
LRG_218t1:c.380A>G
LRG_218:g.11984A>G
LRG_218p1:p.Asn127Ser
NC_000002.11:g.47637246A>G
NM_000251.1:c.380A>G
NM_000251.2:c.380A>G
P43246:p.Asn127Ser
c.380A>G
p.N127S

Protein change:

N127S

Links:

UniProtKB: P43246#VAR_019234; dbSNP: rs17217772

NCBI 1000 Genomes Browser:

rs17217772

Molecular consequence:

NM_000251.3:c.380A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001258281.1:c.182A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Lynch syndrome 1
Synonyms:: COLON CANCER, FAMILIAL NONPOLYPOSIS, TYPE 1; MSH2-Related Hereditary Non-Polyposis Colon Cancer; Lynch syndrome I; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007356; MedGen: C2936783; Orphanet: 144; OMIM: 120435

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000189946	Pathway Genomics	no assertion criteria provided	Benign (Jul 24, 2014)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000430913	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Likely benign (Jan 23, 2018)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 21056691, 25107687, 16395668, 18406877, 16534870, 16237223, 11606497 Citation Link,
SCV000744267	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus	criteria provided, single submitter (ACGS Guidelines, 2013)	Benign (Sep 21, 2015)	germline	clinical testing	Citation Link,
SCV000745632	Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensus	criteria provided, single submitter (ACGS Guidelines, 2013)	Benign (Dec 11, 2016)	germline	clinical testing	Citation Link,
SCV000781768	Center for Human Genetics, Inc, Center for Human Genetics, Inc	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Nov 1, 2016)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004015938	KCCC/NGS Laboratory, Kuwait Cancer Control Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (Jul 7, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

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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	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Prevalence of alterations in DNA mismatch repair genes in patients with young-onset colorectal cancer.

Limburg PJ, Harmsen WS, Chen HH, Gallinger S, Haile RW, Baron JA, Casey G, Woods MO, Thibodeau SN, Lindor NM.

Clin Gastroenterol Hepatol. 2011 Jun;9(6):497-502. doi: 10.1016/j.cgh.2010.10.021. Epub 2010 Nov 5.

PubMed [citation]

PMID:: 21056691
PMCID:: PMC3058119

MLH1 and MSH2 mutation screening in HNPCC families of Hungary - Two new MMR gene mutations.

Tanyi M, Olasz J, Tanyi JL, Tóth L, Antal-Szalmás P, Ress Z, Bubán T, Palatka K, András C, Urbancsek H, Garami Z, Csuka O, Damjanovich L.

Eur J Surg Oncol. 2014 Nov;40(11):1445-52. doi: 10.1016/j.ejso.2014.07.032. Epub 2014 Jul 24.

PubMed [citation]

PMID:: 25107687

See all PubMed Citations (8)

Details of each submission

From Pathway Genomics, SCV000189946.1

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

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

From Illumina Laboratory Services, Illumina, SCV000430913.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.

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

From Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus, SCV000744267.1

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

#	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 Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensus, SCV000745632.1

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

#	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 Center for Human Genetics, Inc, Center for Human Genetics, Inc, SCV000781768.1

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

#	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 KCCC/NGS Laboratory, Kuwait Cancer Control Center, SCV004015938.1

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

#	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: Apr 20, 2024

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