NM_000535.7(PMS2):c.2131A>G (p.Met711Val) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 1, 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:: RCV003760475.2

Allele description [Variation Report for NM_000535.7(PMS2):c.2131A>G (p.Met711Val)]

NM_000535.7(PMS2):c.2131A>G (p.Met711Val)

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.2131A>G (p.Met711Val)

HGVS:

NC_000007.14:g.5982867T>C
NG_008466.1:g.31240A>G
NM_000535.7:c.2131A>GMANE SELECT
NM_001018040.1:c.1726A>G
NM_001322003.2:c.1726A>G
NM_001322004.2:c.1726A>G
NM_001322005.2:c.1726A>G
NM_001322006.2:c.1975A>G
NM_001322007.2:c.1813A>G
NM_001322008.2:c.1813A>G
NM_001322009.2:c.1726A>G
NM_001322010.2:c.1570A>G
NM_001322011.2:c.1198A>G
NM_001322012.2:c.1198A>G
NM_001322013.2:c.1558A>G
NM_001322014.2:c.2131A>G
NM_001322015.2:c.1822A>G
NM_001406866.1:c.2317A>G
NM_001406868.1:c.2155A>G
NM_001406869.1:c.2023A>G
NM_001406870.1:c.1975A>G
NM_001406871.1:c.2131A>G
NM_001406872.1:c.2006+3892A>G
NM_001406873.1:c.1933A>G
NM_001406874.1:c.1963A>G
NM_001406875.1:c.1822A>G
NM_001406876.1:c.1813A>G
NM_001406877.1:c.1822A>G
NM_001406878.1:c.1822A>G
NM_001406879.1:c.1822A>G
NM_001406880.1:c.1822A>G
NM_001406881.1:c.1822A>G
NM_001406882.1:c.1822A>G
NM_001406883.1:c.1813A>G
NM_001406884.1:c.1807A>G
NM_001406885.1:c.1795A>G
NM_001406886.1:c.1765A>G
NM_001406887.1:c.1726A>G
NM_001406888.1:c.1726A>G
NM_001406889.1:c.1726A>G
NM_001406890.1:c.1726A>G
NM_001406891.1:c.1726A>G
NM_001406892.1:c.1726A>G
NM_001406893.1:c.1726A>G
NM_001406894.1:c.1726A>G
NM_001406895.1:c.1726A>G
NM_001406896.1:c.1726A>G
NM_001406897.1:c.1726A>G
NM_001406898.1:c.1726A>G
NM_001406899.1:c.1726A>G
NM_001406900.1:c.1666A>G
NM_001406901.1:c.1657A>G
NM_001406902.1:c.1657A>G
NM_001406903.1:c.1688+3892A>G
NM_001406904.1:c.1618A>G
NM_001406905.1:c.1618A>G
NM_001406906.1:c.1570A>G
NM_001406907.1:c.1570A>G
NM_001406908.1:c.1601+3892A>G
NM_001406909.1:c.1558A>G
NM_001406910.1:c.1601+3892A>G
NM_001406911.1:c.1360A>G
NM_001406912.1:c.928A>G
NP_000526.1:p.Met711Val
NP_000526.2:p.Met711Val
NP_001018050.1:p.Met576Val
NP_001308932.1:p.Met576Val
NP_001308933.1:p.Met576Val
NP_001308934.1:p.Met576Val
NP_001308935.1:p.Met659Val
NP_001308936.1:p.Met605Val
NP_001308937.1:p.Met605Val
NP_001308938.1:p.Met576Val
NP_001308939.1:p.Met524Val
NP_001308940.1:p.Met400Val
NP_001308941.1:p.Met400Val
NP_001308942.1:p.Met520Val
NP_001308943.1:p.Met711Val
NP_001308944.1:p.Met608Val
NP_001393795.1:p.Met773Val
NP_001393797.1:p.Met719Val
NP_001393798.1:p.Met675Val
NP_001393799.1:p.Met659Val
NP_001393800.1:p.Met711Val
NP_001393802.1:p.Met645Val
NP_001393803.1:p.Met655Val
NP_001393804.1:p.Met608Val
NP_001393805.1:p.Met605Val
NP_001393806.1:p.Met608Val
NP_001393807.1:p.Met608Val
NP_001393808.1:p.Met608Val
NP_001393809.1:p.Met608Val
NP_001393810.1:p.Met608Val
NP_001393811.1:p.Met608Val
NP_001393812.1:p.Met605Val
NP_001393813.1:p.Met603Val
NP_001393814.1:p.Met599Val
NP_001393815.1:p.Met589Val
NP_001393816.1:p.Met576Val
NP_001393817.1:p.Met576Val
NP_001393818.1:p.Met576Val
NP_001393819.1:p.Met576Val
NP_001393820.1:p.Met576Val
NP_001393821.1:p.Met576Val
NP_001393822.1:p.Met576Val
NP_001393823.1:p.Met576Val
NP_001393824.1:p.Met576Val
NP_001393825.1:p.Met576Val
NP_001393826.1:p.Met576Val
NP_001393827.1:p.Met576Val
NP_001393828.1:p.Met576Val
NP_001393829.1:p.Met556Val
NP_001393830.1:p.Met553Val
NP_001393831.1:p.Met553Val
NP_001393833.1:p.Met540Val
NP_001393834.1:p.Met540Val
NP_001393835.1:p.Met524Val
NP_001393836.1:p.Met524Val
NP_001393838.1:p.Met520Val
NP_001393840.1:p.Met454Val
NP_001393841.1:p.Met310Val
LRG_161t1:c.2131A>G
LRG_161:g.31240A>G
LRG_161p1:p.Met711Val
NC_000007.13:g.6022498T>C
NM_000535.5:c.2131A>G
NR_003085.2:n.2213A>G
NR_136154.1:n.2218A>G

Protein change:

M310V

Molecular consequence:

NM_001406872.1:c.2006+3892A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001406903.1:c.1688+3892A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001406908.1:c.1601+3892A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001406910.1:c.1601+3892A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000535.7:c.2131A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001018040.1:c.1726A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322003.2:c.1726A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322004.2:c.1726A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322005.2:c.1726A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322006.2:c.1975A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322007.2:c.1813A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322008.2:c.1813A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322009.2:c.1726A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322010.2:c.1570A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322011.2:c.1198A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322012.2:c.1198A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322013.2:c.1558A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322014.2:c.2131A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322015.2:c.1822A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406866.1:c.2317A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406868.1:c.2155A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406869.1:c.2023A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406870.1:c.1975A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406871.1:c.2131A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406873.1:c.1933A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406874.1:c.1963A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406875.1:c.1822A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406876.1:c.1813A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406877.1:c.1822A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406878.1:c.1822A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406879.1:c.1822A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406880.1:c.1822A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406881.1:c.1822A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406882.1:c.1822A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406883.1:c.1813A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406884.1:c.1807A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406885.1:c.1795A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406886.1:c.1765A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406887.1:c.1726A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406888.1:c.1726A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406889.1:c.1726A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406890.1:c.1726A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406891.1:c.1726A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406892.1:c.1726A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406893.1:c.1726A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406894.1:c.1726A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406895.1:c.1726A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406896.1:c.1726A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406897.1:c.1726A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406898.1:c.1726A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406899.1:c.1726A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406900.1:c.1666A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406901.1:c.1657A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406902.1:c.1657A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406904.1:c.1618A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406905.1:c.1618A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406906.1:c.1570A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406907.1:c.1570A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406909.1:c.1558A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406911.1:c.1360A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406912.1:c.928A>G - missense variant - [Sequence Ontology: SO:0001583]
NR_136154.1:n.2218A>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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Nucleotide
SRX5066987 (1)
SRA

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004540422	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 1, 2023)	germline	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

SCV004540422

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 1, 2023)

germline

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

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV004540422.1

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

Description

This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 711 of the PMS2 protein (p.Met711Val). 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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PMS2 protein function. 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.

#	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

Last Updated: Sep 29, 2024

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