NM_000251.3(MSH2):c.126C>G (p.Phe42Leu) AND Lynch syndrome 1

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Sep 25, 2024
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:: RCV004567210.2

Allele description [Variation Report for NM_000251.3(MSH2):c.126C>G (p.Phe42Leu)]

NM_000251.3(MSH2):c.126C>G (p.Phe42Leu)

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.126C>G (p.Phe42Leu)

Other names:

p.F42L:TTC>TTG

HGVS:

NC_000002.12:g.47403317C>G
NG_007110.2:g.5194C>G
NM_000251.3:c.126C>GMANE SELECT
NM_001258281.1:c.-30-43C>G
NP_000242.1:p.Phe42Leu
NP_000242.1:p.Phe42Leu
LRG_218t1:c.126C>G
LRG_218:g.5194C>G
LRG_218p1:p.Phe42Leu
NC_000002.11:g.47630456C>G
NM_000251.1:c.126C>G
NM_000251.2:c.126C>G
p.F42L

Protein change:

F42L

Links:

dbSNP: rs730881766

NCBI 1000 Genomes Browser:

rs730881766

Molecular consequence:

NM_001258281.1:c.-30-43C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000251.3:c.126C>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
SCV005053468	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Feb 5, 2024)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005403878	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Likely benign (Sep 25, 2024)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005053468

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Feb 5, 2024)

unknown

clinical testing

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

SCV005403878

Myriad Genetics, Inc.

criteria provided, single submitter

(Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))

Likely benign
(Sep 25, 2024)

unknown

clinical testing

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

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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

Classification of genetic variants in genes associated with Lynch syndrome using a clinical history weighting algorithm.

Morris B, Hughes E, Rosenthal E, Gutin A, Bowles KR.

BMC Genet. 2016 Jul 1;17(1):99. doi: 10.1186/s12863-016-0407-0.

PubMed [citation]

PMID:: 27363726
PMCID:: PMC4929734

Details of each submission

From Baylor Genetics, SCV005053468.1

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Myriad Genetics, Inc., SCV005403878.1

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

Description

This variant is considered likely benign. This variant is strongly associated with less severe personal and family histories of cancer, typical for individuals without pathogenic variants in this gene [PMID: 27363726].

#	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: Nov 24, 2024

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