NM_000251.3(MSH2):c.174C>G (p.Phe58Leu) AND Lynch syndrome 1

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Aug 20, 2023
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:: RCV003153620.3

Allele description [Variation Report for NM_000251.3(MSH2):c.174C>G (p.Phe58Leu)]

NM_000251.3(MSH2):c.174C>G (p.Phe58Leu)

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.174C>G (p.Phe58Leu)

HGVS:

NC_000002.12:g.47403365C>G
NG_007110.2:g.5242C>G
NM_000251.3:c.174C>GMANE SELECT
NM_001258281.1:c.-25C>G
NP_000242.1:p.Phe58Leu
NP_000242.1:p.Phe58Leu
LRG_218t1:c.174C>G
LRG_218:g.5242C>G
LRG_218p1:p.Phe58Leu
NC_000002.11:g.47630504C>G
NM_000251.1:c.174C>G
NM_000251.2:c.174C>G

Protein change:

F58L

Links:

dbSNP: rs372189599

NCBI 1000 Genomes Browser:

rs372189599

Molecular consequence:

NM_001258281.1:c.-25C>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000251.3:c.174C>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

Recent activity

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protein FAM241B isoform X2 [Homo sapiens]
protein FAM241B isoform X2 [Homo sapiens]
gi|2462517441|ref|XP_054220985.1|

Protein
Homo sapiens vascular endothelial growth factor gene, complete cds
Homo sapiens vascular endothelial growth factor gene, complete cds
gi|1036032453|gb|AH001553.2|

Nucleotide
OMIM Links for GEO Profiles (Select 122102382) (1)
OMIM
GSE197120[ACCN] AND gsm[ETYP] (13)
GEO DataSets
PMC Links for GEO Profiles (Select 122088618) (75)
PMC

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003843019	St. Jude Molecular Pathology, St. Jude Children's Research Hospital	criteria provided, single submitter (St. Jude Assertion Criteria 2020)	Uncertain significance (Jan 27, 2023)	germline	clinical testing	Citation Link,
SCV004196298	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Aug 20, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003843019

St. Jude Molecular Pathology, St. Jude Children's Research Hospital

criteria provided, single submitter

(St. Jude Assertion Criteria 2020)

Uncertain significance
(Jan 27, 2023)

germline

clinical testing

Citation Link,

SCV004196298

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Aug 20, 2023)

unknown

clinical testing

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

Help

Summary from all submissions

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

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 St. Jude Molecular Pathology, St. Jude Children's Research Hospital, SCV003843019.1

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

Description

The MSH2 c.174C>G (p.Phe58Leu) missense change has a maximum subpopulation frequency of 0.0090% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org). The in silico tool REVEL predicts a deleterious effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. This variant has been reported in the literature in at least one individual with suspected Lynch syndrome (PMID: 25980754). To our knowledge, this variant has not been reported in individual(s) with constitutional mismatch repair deficiency. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.

#	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 Baylor Genetics, SCV004196298.1

#	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

Last Updated: Sep 29, 2024

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