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NM_000535.7(PMS2):c.2083A>G (p.Ile695Val) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Sep 24, 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:
RCV002625264.2

Allele description

NM_000535.7(PMS2):c.2083A>G (p.Ile695Val)

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.2083A>G (p.Ile695Val)
HGVS:
  • NC_000007.14:g.5982915T>C
  • NG_008466.1:g.31192A>G
  • NM_000535.7:c.2083A>GMANE SELECT
  • NM_001018040.1:c.1678A>G
  • NM_001322003.2:c.1678A>G
  • NM_001322004.2:c.1678A>G
  • NM_001322005.2:c.1678A>G
  • NM_001322006.2:c.1927A>G
  • NM_001322007.2:c.1765A>G
  • NM_001322008.2:c.1765A>G
  • NM_001322009.2:c.1678A>G
  • NM_001322010.2:c.1522A>G
  • NM_001322011.2:c.1150A>G
  • NM_001322012.2:c.1150A>G
  • NM_001322013.2:c.1510A>G
  • NM_001322014.2:c.2083A>G
  • NM_001322015.2:c.1774A>G
  • NM_001406866.1:c.2269A>G
  • NM_001406868.1:c.2107A>G
  • NM_001406869.1:c.1975A>G
  • NM_001406870.1:c.1927A>G
  • NM_001406871.1:c.2083A>G
  • NM_001406873.1:c.1885A>G
  • NM_001406874.1:c.1915A>G
  • NM_001406875.1:c.1774A>G
  • NM_001406876.1:c.1765A>G
  • NM_001406877.1:c.1774A>G
  • NM_001406878.1:c.1774A>G
  • NM_001406879.1:c.1774A>G
  • NM_001406880.1:c.1774A>G
  • NM_001406881.1:c.1774A>G
  • NM_001406882.1:c.1774A>G
  • NM_001406883.1:c.1765A>G
  • NM_001406884.1:c.1759A>G
  • NM_001406885.1:c.1747A>G
  • NM_001406886.1:c.1717A>G
  • NM_001406887.1:c.1678A>G
  • NM_001406888.1:c.1678A>G
  • NM_001406889.1:c.1678A>G
  • NM_001406890.1:c.1678A>G
  • NM_001406891.1:c.1678A>G
  • NM_001406892.1:c.1678A>G
  • NM_001406893.1:c.1678A>G
  • NM_001406894.1:c.1678A>G
  • NM_001406895.1:c.1678A>G
  • NM_001406896.1:c.1678A>G
  • NM_001406897.1:c.1678A>G
  • NM_001406898.1:c.1678A>G
  • NM_001406899.1:c.1678A>G
  • NM_001406900.1:c.1618A>G
  • NM_001406901.1:c.1609A>G
  • NM_001406902.1:c.1609A>G
  • NM_001406904.1:c.1570A>G
  • NM_001406905.1:c.1570A>G
  • NM_001406906.1:c.1522A>G
  • NM_001406907.1:c.1522A>G
  • NM_001406909.1:c.1510A>G
  • NM_001406911.1:c.1312A>G
  • NM_001406912.1:c.880A>G
  • NP_000526.1:p.Ile695Val
  • NP_000526.2:p.Ile695Val
  • NP_001018050.1:p.Ile560Val
  • NP_001308932.1:p.Ile560Val
  • NP_001308933.1:p.Ile560Val
  • NP_001308934.1:p.Ile560Val
  • NP_001308935.1:p.Ile643Val
  • NP_001308936.1:p.Ile589Val
  • NP_001308937.1:p.Ile589Val
  • NP_001308938.1:p.Ile560Val
  • NP_001308939.1:p.Ile508Val
  • NP_001308940.1:p.Ile384Val
  • NP_001308941.1:p.Ile384Val
  • NP_001308942.1:p.Ile504Val
  • NP_001308943.1:p.Ile695Val
  • NP_001308944.1:p.Ile592Val
  • NP_001393795.1:p.Ile757Val
  • NP_001393797.1:p.Ile703Val
  • NP_001393798.1:p.Ile659Val
  • NP_001393799.1:p.Ile643Val
  • NP_001393800.1:p.Ile695Val
  • NP_001393802.1:p.Ile629Val
  • NP_001393803.1:p.Ile639Val
  • NP_001393804.1:p.Ile592Val
  • NP_001393805.1:p.Ile589Val
  • NP_001393806.1:p.Ile592Val
  • NP_001393807.1:p.Ile592Val
  • NP_001393808.1:p.Ile592Val
  • NP_001393809.1:p.Ile592Val
  • NP_001393810.1:p.Ile592Val
  • NP_001393811.1:p.Ile592Val
  • NP_001393812.1:p.Ile589Val
  • NP_001393813.1:p.Ile587Val
  • NP_001393814.1:p.Ile583Val
  • NP_001393815.1:p.Ile573Val
  • NP_001393816.1:p.Ile560Val
  • NP_001393817.1:p.Ile560Val
  • NP_001393818.1:p.Ile560Val
  • NP_001393819.1:p.Ile560Val
  • NP_001393820.1:p.Ile560Val
  • NP_001393821.1:p.Ile560Val
  • NP_001393822.1:p.Ile560Val
  • NP_001393823.1:p.Ile560Val
  • NP_001393824.1:p.Ile560Val
  • NP_001393825.1:p.Ile560Val
  • NP_001393826.1:p.Ile560Val
  • NP_001393827.1:p.Ile560Val
  • NP_001393828.1:p.Ile560Val
  • NP_001393829.1:p.Ile540Val
  • NP_001393830.1:p.Ile537Val
  • NP_001393831.1:p.Ile537Val
  • NP_001393833.1:p.Ile524Val
  • NP_001393834.1:p.Ile524Val
  • NP_001393835.1:p.Ile508Val
  • NP_001393836.1:p.Ile508Val
  • NP_001393838.1:p.Ile504Val
  • NP_001393840.1:p.Ile438Val
  • NP_001393841.1:p.Ile294Val
  • LRG_161t1:c.2083A>G
  • LRG_161:g.31192A>G
  • LRG_161p1:p.Ile695Val
  • NC_000007.13:g.6022546T>C
  • NM_000535.5:c.2083A>G
  • NR_003085.2:n.2165A>G
  • NR_136154.1:n.2170A>G
Protein change:
I294V
Molecular consequence:
  • NM_000535.7:c.2083A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001018040.1:c.1678A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322003.2:c.1678A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322004.2:c.1678A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322005.2:c.1678A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322006.2:c.1927A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322007.2:c.1765A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322008.2:c.1765A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322009.2:c.1678A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322010.2:c.1522A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322011.2:c.1150A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322012.2:c.1150A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322013.2:c.1510A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322014.2:c.2083A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322015.2:c.1774A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406866.1:c.2269A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406868.1:c.2107A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406869.1:c.1975A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406870.1:c.1927A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406871.1:c.2083A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406873.1:c.1885A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406874.1:c.1915A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406875.1:c.1774A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406876.1:c.1765A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406877.1:c.1774A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406878.1:c.1774A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406879.1:c.1774A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406880.1:c.1774A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406881.1:c.1774A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406882.1:c.1774A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406883.1:c.1765A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406884.1:c.1759A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406885.1:c.1747A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406886.1:c.1717A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406887.1:c.1678A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406888.1:c.1678A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406889.1:c.1678A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406890.1:c.1678A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406891.1:c.1678A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406892.1:c.1678A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406893.1:c.1678A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406894.1:c.1678A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406895.1:c.1678A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406896.1:c.1678A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406897.1:c.1678A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406898.1:c.1678A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406899.1:c.1678A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406900.1:c.1618A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406901.1:c.1609A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406902.1:c.1609A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406904.1:c.1570A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406905.1:c.1570A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406906.1:c.1522A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406907.1:c.1522A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406909.1:c.1510A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406911.1:c.1312A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406912.1:c.880A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NR_136154.1:n.2170A>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
SCV003521016Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Sep 24, 2022) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

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 Invitae, SCV003521016.2

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

Description

This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 695 of the PMS2 protein (p.Ile695Val). The frequency data for this variant in the population databases (gnomAD) is considered unreliable due to the presence of homologous sequence, such as pseudogenes or paralogs, in the genome. 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. This variant has not been reported in the literature in individuals affected with PMS2-related conditions. 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 not expected to disrupt PMS2 protein function.

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

Last Updated: May 7, 2024