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NM_000535.7(PMS2):c.343T>G (p.Cys115Gly) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Nov 11, 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:
RCV003761165.2

Allele description [Variation Report for NM_000535.7(PMS2):c.343T>G (p.Cys115Gly)]

NM_000535.7(PMS2):c.343T>G (p.Cys115Gly)

Gene:
PMS2:PMS1 homolog 2, mismatch repair system component [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7p22.1
Genomic location:
Preferred name:
NM_000535.7(PMS2):c.343T>G (p.Cys115Gly)
HGVS:
  • NC_000007.14:g.6003700A>C
  • NG_008466.1:g.10407T>G
  • NM_000535.7:c.343T>GMANE SELECT
  • NM_001018040.1:c.-63T>G
  • NM_001322003.2:c.-63T>G
  • NM_001322004.2:c.-63T>G
  • NM_001322005.2:c.-63T>G
  • NM_001322006.2:c.343T>G
  • NM_001322007.2:c.35+272T>G
  • NM_001322008.2:c.35+272T>G
  • NM_001322009.2:c.-63T>G
  • NM_001322010.2:c.-63T>G
  • NM_001322011.2:c.-542T>G
  • NM_001322012.2:c.-542T>G
  • NM_001322013.2:c.-63T>G
  • NM_001322014.2:c.343T>G
  • NM_001322015.2:c.-142T>G
  • NM_001406866.1:c.529T>G
  • NM_001406868.1:c.367T>G
  • NM_001406869.1:c.343T>G
  • NM_001406870.1:c.343T>G
  • NM_001406871.1:c.343T>G
  • NM_001406872.1:c.343T>G
  • NM_001406873.1:c.343T>G
  • NM_001406874.1:c.343T>G
  • NM_001406875.1:c.-142T>G
  • NM_001406876.1:c.35+272T>G
  • NM_001406877.1:c.-142T>G
  • NM_001406878.1:c.-142T>G
  • NM_001406879.1:c.-142T>G
  • NM_001406880.1:c.-132+43T>G
  • NM_001406881.1:c.-132+272T>G
  • NM_001406882.1:c.-142T>G
  • NM_001406883.1:c.35+272T>G
  • NM_001406884.1:c.343T>G
  • NM_001406885.1:c.250+272T>G
  • NM_001406886.1:c.343T>G
  • NM_001406887.1:c.-63T>G
  • NM_001406888.1:c.-53+43T>G
  • NM_001406889.1:c.-53+43T>G
  • NM_001406890.1:c.-53T>G
  • NM_001406891.1:c.-63T>G
  • NM_001406892.1:c.-53+43T>G
  • NM_001406893.1:c.-63T>G
  • NM_001406894.1:c.-53+43T>G
  • NM_001406895.1:c.-53+43T>G
  • NM_001406896.1:c.-52-1064T>G
  • NM_001406897.1:c.-63T>G
  • NM_001406898.1:c.-63T>G
  • NM_001406899.1:c.-53+43T>G
  • NM_001406900.1:c.-132+272T>G
  • NM_001406901.1:c.35+272T>G
  • NM_001406902.1:c.35+272T>G
  • NM_001406903.1:c.35+272T>G
  • NM_001406904.1:c.-53+43T>G
  • NM_001406905.1:c.-63T>G
  • NM_001406906.1:c.-63T>G
  • NM_001406907.1:c.-53+43T>G
  • NM_001406908.1:c.-63T>G
  • NM_001406909.1:c.-53+43T>G
  • NM_001406910.1:c.-63T>G
  • NM_001406911.1:c.-63T>G
  • NM_001406912.1:c.343T>G
  • NP_000526.1:p.Cys115Gly
  • NP_000526.2:p.Cys115Gly
  • NP_001308935.1:p.Cys115Gly
  • NP_001308943.1:p.Cys115Gly
  • NP_001393795.1:p.Cys177Gly
  • NP_001393797.1:p.Cys123Gly
  • NP_001393798.1:p.Cys115Gly
  • NP_001393799.1:p.Cys115Gly
  • NP_001393800.1:p.Cys115Gly
  • NP_001393801.1:p.Cys115Gly
  • NP_001393802.1:p.Cys115Gly
  • NP_001393803.1:p.Cys115Gly
  • NP_001393813.1:p.Cys115Gly
  • NP_001393815.1:p.Cys115Gly
  • NP_001393841.1:p.Cys115Gly
  • LRG_161t1:c.343T>G
  • LRG_161:g.10407T>G
  • LRG_161p1:p.Cys115Gly
  • NC_000007.13:g.6043331A>C
  • NM_000535.5:c.343T>G
  • NR_003085.2:n.425T>G
  • NR_136154.1:n.430T>G
Protein change:
C115G
Molecular consequence:
  • NM_001322003.2:c.-63T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322004.2:c.-63T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322005.2:c.-63T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322009.2:c.-63T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322010.2:c.-63T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322011.2:c.-542T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322012.2:c.-542T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322013.2:c.-63T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322015.2:c.-142T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001406875.1:c.-142T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001406877.1:c.-142T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001406878.1:c.-142T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001406879.1:c.-142T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001406882.1:c.-142T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001406887.1:c.-63T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001406890.1:c.-53T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001406891.1:c.-63T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001406893.1:c.-63T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001406897.1:c.-63T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001406898.1:c.-63T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001406905.1:c.-63T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001406906.1:c.-63T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001406908.1:c.-63T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001406910.1:c.-63T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001406911.1:c.-63T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322007.2:c.35+272T>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001322008.2:c.35+272T>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001406876.1:c.35+272T>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001406880.1:c.-132+43T>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001406881.1:c.-132+272T>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001406883.1:c.35+272T>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001406885.1:c.250+272T>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001406888.1:c.-53+43T>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001406889.1:c.-53+43T>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001406892.1:c.-53+43T>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001406894.1:c.-53+43T>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001406895.1:c.-53+43T>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001406896.1:c.-52-1064T>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001406899.1:c.-53+43T>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001406900.1:c.-132+272T>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001406901.1:c.35+272T>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001406902.1:c.35+272T>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001406903.1:c.35+272T>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001406904.1:c.-53+43T>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001406907.1:c.-53+43T>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001406909.1:c.-53+43T>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000535.7:c.343T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322006.2:c.343T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322014.2:c.343T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406866.1:c.529T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406868.1:c.367T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406869.1:c.343T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406870.1:c.343T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406871.1:c.343T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406872.1:c.343T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406873.1:c.343T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406874.1:c.343T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406884.1:c.343T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406886.1:c.343T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406912.1:c.343T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NR_136154.1:n.430T>G - 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
SCV004562009Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Nov 11, 2023) 		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

Comprehensive Mutation Analysis of PMS2 in a Large Cohort of Probands Suspected of Lynch Syndrome or Constitutional Mismatch Repair Deficiency Syndrome.

van der Klift HM, Mensenkamp AR, Drost M, Bik EC, Vos YJ, Gille HJ, Redeker BE, Tiersma Y, Zonneveld JB, García EG, Letteboer TG, Olderode-Berends MJ, van Hest LP, van Os TA, Verhoef S, Wagner A, van Asperen CJ, Ten Broeke SW, Hes FJ, de Wind N, Nielsen M, Devilee P, et al.

Hum Mutat. 2016 Nov;37(11):1162-1179. doi: 10.1002/humu.23052. Epub 2016 Aug 21.

PubMed [citation]
PMID:
27435373

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, SCV004562009.1

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

Description

This sequence change replaces cysteine, which is neutral and slightly polar, with glycine, which is neutral and non-polar, at codon 115 of the PMS2 protein (p.Cys115Gly). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with PMS2-related conditions (PMID: 27435373). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PMS2 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects PMS2 function (PMID: 27435373). 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.

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

Last Updated: Sep 29, 2024