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NM_000251.3(MSH2):c.144G>T (p.Glu48Asp) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Dec 3, 2022
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:
RCV003760563.2

Allele description [Variation Report for NM_000251.3(MSH2):c.144G>T (p.Glu48Asp)]

NM_000251.3(MSH2):c.144G>T (p.Glu48Asp)

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.144G>T (p.Glu48Asp)
HGVS:
  • NC_000002.12:g.47403335G>T
  • NG_007110.2:g.5212G>T
  • NG_095167.1:g.539G>T
  • NM_000251.3:c.144G>TMANE SELECT
  • NM_001258281.1:c.-30-25G>T
  • NM_001406631.1:c.144G>T
  • NM_001406632.1:c.144G>T
  • NM_001406633.1:c.144G>T
  • NM_001406634.1:c.144G>T
  • NM_001406635.1:c.144G>T
  • NM_001406636.1:c.144G>T
  • NM_001406637.1:c.144G>T
  • NM_001406638.1:c.144G>T
  • NM_001406639.1:c.144G>T
  • NM_001406640.1:c.144G>T
  • NM_001406641.1:c.144G>T
  • NM_001406642.1:c.144G>T
  • NM_001406643.1:c.144G>T
  • NM_001406644.1:c.144G>T
  • NM_001406645.1:c.144G>T
  • NM_001406646.1:c.144G>T
  • NM_001406647.1:c.144G>T
  • NM_001406648.1:c.144G>T
  • NM_001406649.1:c.144G>T
  • NM_001406650.1:c.144G>T
  • NM_001406651.1:c.144G>T
  • NM_001406652.1:c.144G>T
  • NM_001406653.1:c.144G>T
  • NM_001406654.1:c.-197G>T
  • NM_001406655.1:c.144G>T
  • NM_001406656.1:c.-852G>T
  • NM_001406657.1:c.144G>T
  • NM_001406658.1:c.-1175G>T
  • NM_001406659.1:c.-1325G>T
  • NM_001406660.1:c.-1522G>T
  • NM_001406661.1:c.-1477G>T
  • NM_001406662.1:c.-1394G>T
  • NM_001406666.1:c.144G>T
  • NM_001406669.1:c.-1325G>T
  • NM_001406672.1:c.144G>T
  • NM_001406674.1:c.144G>T
  • NP_000242.1:p.Glu48Asp
  • NP_000242.1:p.Glu48Asp
  • NP_001393560.1:p.Glu48Asp
  • NP_001393561.1:p.Glu48Asp
  • NP_001393562.1:p.Glu48Asp
  • NP_001393563.1:p.Glu48Asp
  • NP_001393564.1:p.Glu48Asp
  • NP_001393565.1:p.Glu48Asp
  • NP_001393566.1:p.Glu48Asp
  • NP_001393567.1:p.Glu48Asp
  • NP_001393568.1:p.Glu48Asp
  • NP_001393569.1:p.Glu48Asp
  • NP_001393570.1:p.Glu48Asp
  • NP_001393571.1:p.Glu48Asp
  • NP_001393572.1:p.Glu48Asp
  • NP_001393573.1:p.Glu48Asp
  • NP_001393574.1:p.Glu48Asp
  • NP_001393575.1:p.Glu48Asp
  • NP_001393576.1:p.Glu48Asp
  • NP_001393577.1:p.Glu48Asp
  • NP_001393578.1:p.Glu48Asp
  • NP_001393579.1:p.Glu48Asp
  • NP_001393580.1:p.Glu48Asp
  • NP_001393581.1:p.Glu48Asp
  • NP_001393582.1:p.Glu48Asp
  • NP_001393584.1:p.Glu48Asp
  • NP_001393586.1:p.Glu48Asp
  • NP_001393595.1:p.Glu48Asp
  • NP_001393601.1:p.Glu48Asp
  • NP_001393603.1:p.Glu48Asp
  • LRG_218t1:c.144G>T
  • LRG_218:g.5212G>T
  • LRG_218p1:p.Glu48Asp
  • NC_000002.11:g.47630474G>T
  • NM_000251.2:c.144G>T
  • NR_176230.1:n.180G>T
  • NR_176231.1:n.180G>T
  • NR_176232.1:n.180G>T
  • NR_176233.1:n.180G>T
  • NR_176234.1:n.180G>T
  • NR_176235.1:n.180G>T
  • NR_176236.1:n.180G>T
  • NR_176237.1:n.180G>T
  • NR_176238.1:n.180G>T
  • NR_176239.1:n.180G>T
  • NR_176240.1:n.180G>T
  • NR_176241.1:n.180G>T
  • NR_176242.1:n.180G>T
  • NR_176243.1:n.180G>T
  • NR_176244.1:n.180G>T
  • NR_176245.1:n.180G>T
  • NR_176246.1:n.180G>T
  • NR_176247.1:n.180G>T
  • NR_176248.1:n.180G>T
  • NR_176249.1:n.180G>T
  • NR_176250.1:n.180G>T
Protein change:
E48D
Molecular consequence:
  • NM_001406654.1:c.-197G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001406656.1:c.-852G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001406658.1:c.-1175G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001406659.1:c.-1325G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001406660.1:c.-1522G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001406661.1:c.-1477G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001406662.1:c.-1394G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001406669.1:c.-1325G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001258281.1:c.-30-25G>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000251.3:c.144G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406631.1:c.144G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406632.1:c.144G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406633.1:c.144G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406634.1:c.144G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406635.1:c.144G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406636.1:c.144G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406637.1:c.144G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406638.1:c.144G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406639.1:c.144G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406640.1:c.144G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406641.1:c.144G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406642.1:c.144G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406643.1:c.144G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406644.1:c.144G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406645.1:c.144G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406646.1:c.144G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406647.1:c.144G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406648.1:c.144G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406649.1:c.144G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406650.1:c.144G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406651.1:c.144G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406652.1:c.144G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406653.1:c.144G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406655.1:c.144G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406657.1:c.144G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406666.1:c.144G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406672.1:c.144G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406674.1:c.144G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_176230.1:n.180G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_176231.1:n.180G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_176232.1:n.180G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_176233.1:n.180G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_176234.1:n.180G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_176235.1:n.180G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_176236.1:n.180G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_176237.1:n.180G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_176238.1:n.180G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_176239.1:n.180G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_176240.1:n.180G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_176241.1:n.180G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_176242.1:n.180G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_176243.1:n.180G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_176244.1:n.180G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_176245.1:n.180G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_176246.1:n.180G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_176247.1:n.180G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_176248.1:n.180G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_176249.1:n.180G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_176250.1:n.180G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Hereditary nonpolyposis colorectal neoplasms
Identifiers:
MeSH: D003123; MedGen: C0009405

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004550766Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Dec 3, 2022) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004550766.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 33357406) indicates that this missense variant is not expected to disrupt MSH2 function. This variant has not been reported in the literature in individuals affected with MSH2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 48 of the MSH2 protein (p.Glu48Asp).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024