NM_000251.3(MSH2):c.219G>C (p.Lys73Asn) AND Lynch syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 4, 2023
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:: RCV004013280.2

Allele description [Variation Report for NM_000251.3(MSH2):c.219G>C (p.Lys73Asn)]

NM_000251.3(MSH2):c.219G>C (p.Lys73Asn)

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.219G>C (p.Lys73Asn)

HGVS:

NC_000002.12:g.47408408G>C
NG_007110.2:g.10285G>C
NM_000251.3:c.219G>CMANE SELECT
NM_001258281.1:c.21G>C
NM_001406631.1:c.219G>C
NM_001406632.1:c.219G>C
NM_001406633.1:c.219G>C
NM_001406634.1:c.219G>C
NM_001406635.1:c.219G>C
NM_001406636.1:c.219G>C
NM_001406637.1:c.219G>C
NM_001406638.1:c.219G>C
NM_001406639.1:c.219G>C
NM_001406640.1:c.219G>C
NM_001406641.1:c.219G>C
NM_001406642.1:c.219G>C
NM_001406643.1:c.219G>C
NM_001406644.1:c.219G>C
NM_001406645.1:c.219G>C
NM_001406646.1:c.219G>C
NM_001406647.1:c.219G>C
NM_001406648.1:c.219G>C
NM_001406649.1:c.219G>C
NM_001406650.1:c.219G>C
NM_001406651.1:c.219G>C
NM_001406652.1:c.219G>C
NM_001406653.1:c.212-53G>C
NM_001406654.1:c.-129-73G>C
NM_001406655.1:c.219G>C
NM_001406656.1:c.-777G>C
NM_001406657.1:c.219G>C
NM_001406658.1:c.-1100G>C
NM_001406659.1:c.-1250G>C
NM_001406660.1:c.-1447G>C
NM_001406661.1:c.-1402G>C
NM_001406662.1:c.-1319G>C
NM_001406666.1:c.219G>C
NM_001406669.1:c.-1250G>C
NM_001406672.1:c.219G>C
NM_001406674.1:c.219G>C
NP_000242.1:p.Lys73Asn
NP_000242.1:p.Lys73Asn
NP_001245210.1:p.Lys7Asn
NP_001393560.1:p.Lys73Asn
NP_001393561.1:p.Lys73Asn
NP_001393562.1:p.Lys73Asn
NP_001393563.1:p.Lys73Asn
NP_001393564.1:p.Lys73Asn
NP_001393565.1:p.Lys73Asn
NP_001393566.1:p.Lys73Asn
NP_001393567.1:p.Lys73Asn
NP_001393568.1:p.Lys73Asn
NP_001393569.1:p.Lys73Asn
NP_001393570.1:p.Lys73Asn
NP_001393571.1:p.Lys73Asn
NP_001393572.1:p.Lys73Asn
NP_001393573.1:p.Lys73Asn
NP_001393574.1:p.Lys73Asn
NP_001393575.1:p.Lys73Asn
NP_001393576.1:p.Lys73Asn
NP_001393577.1:p.Lys73Asn
NP_001393578.1:p.Lys73Asn
NP_001393579.1:p.Lys73Asn
NP_001393580.1:p.Lys73Asn
NP_001393581.1:p.Lys73Asn
NP_001393584.1:p.Lys73Asn
NP_001393586.1:p.Lys73Asn
NP_001393595.1:p.Lys73Asn
NP_001393601.1:p.Lys73Asn
NP_001393603.1:p.Lys73Asn
LRG_218t1:c.219G>C
LRG_218:g.10285G>C
LRG_218p1:p.Lys73Asn
NC_000002.11:g.47635547G>C
NM_000251.2:c.219G>C
NR_176230.1:n.255G>C
NR_176231.1:n.255G>C
NR_176232.1:n.255G>C
NR_176234.1:n.255G>C
NR_176235.1:n.255G>C
NR_176236.1:n.255G>C
NR_176237.1:n.255G>C
NR_176238.1:n.255G>C
NR_176239.1:n.255G>C
NR_176240.1:n.255G>C
NR_176241.1:n.255G>C
NR_176242.1:n.255G>C
NR_176243.1:n.255G>C
NR_176244.1:n.255G>C
NR_176245.1:n.255G>C
NR_176246.1:n.255G>C
NR_176247.1:n.255G>C
NR_176248.1:n.255G>C
NR_176249.1:n.255G>C
NR_176250.1:n.255G>C

Protein change:

K73N

Molecular consequence:

NM_001406656.1:c.-777G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001406658.1:c.-1100G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001406659.1:c.-1250G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001406660.1:c.-1447G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001406661.1:c.-1402G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001406662.1:c.-1319G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001406669.1:c.-1250G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001406653.1:c.212-53G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001406654.1:c.-129-73G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_000251.3:c.219G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001258281.1:c.21G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406631.1:c.219G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406632.1:c.219G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406633.1:c.219G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406634.1:c.219G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406635.1:c.219G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406636.1:c.219G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406637.1:c.219G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406638.1:c.219G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406639.1:c.219G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406640.1:c.219G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406641.1:c.219G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406642.1:c.219G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406643.1:c.219G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406644.1:c.219G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406645.1:c.219G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406646.1:c.219G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406647.1:c.219G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406648.1:c.219G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406649.1:c.219G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406650.1:c.219G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406651.1:c.219G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406652.1:c.219G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406655.1:c.219G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406657.1:c.219G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406666.1:c.219G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406672.1:c.219G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406674.1:c.219G>C - missense variant - [Sequence Ontology: SO:0001583]
NR_176230.1:n.255G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176231.1:n.255G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176232.1:n.255G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176234.1:n.255G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176235.1:n.255G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176236.1:n.255G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176237.1:n.255G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176238.1:n.255G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176239.1:n.255G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176240.1:n.255G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176241.1:n.255G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176242.1:n.255G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176243.1:n.255G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176244.1:n.255G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176245.1:n.255G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176246.1:n.255G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176247.1:n.255G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176248.1:n.255G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176249.1:n.255G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176250.1:n.255G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

Name:: Lynch syndrome
Identifiers:: MONDO: MONDO:0005835; MedGen: C4552100

Recent activity

Clear Turn Off Turn On

contactin-6 isoform 1 precursor [Homo sapiens]
contactin-6 isoform 1 precursor [Homo sapiens]
gi|7657361|ref|NP_055276.1|

Protein

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004833025	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain Significance (May 4, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 33357406, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004833025

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain Significance
(May 4, 2023)

germline

clinical testing

PubMed (2)
[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	unknown	1	not provided	not provided	108544	not provided	clinical testing

Citations

PubMed

Massively parallel functional testing of MSH2 missense variants conferring Lynch syndrome risk.

Jia X, Burugula BB, Chen V, Lemons RM, Jayakody S, Maksutova M, Kitzman JO.

Am J Hum Genet. 2021 Jan 7;108(1):163-175. doi: 10.1016/j.ajhg.2020.12.003. Epub 2020 Dec 23.

PubMed [citation]

PMID:: 33357406
PMCID:: PMC7820803

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 All of Us Research Program, National Institutes of Health, SCV004833025.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (2)

Description

This missense variant replaces lysine with asparagine at codon 73 of the MSH2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). This variant does not impact MSH2 function in a 6-thioguanine sensitivity assay in haploid human cells (internally defined LOF score threshold <= -1.32, PMID: 33357406). To our knowledge, this variant has not been reported in individuals affected with MSH2-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	108544	not provided	not provided		1	not provided	not provided	not provided

Last Updated: May 7, 2024

ClinVar

Relating variation to medicine