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 starscriteria provided, single submitter
- Somatic classification
of clinical impact: - None
- Review status:
- (0/4) 0 stars out of maximum of 4 starsno assertion criteria provided
- Somatic classification
of oncogenicity: - None
- Review status:
- (0/4) 0 stars out of maximum of 4 starsno assertion criteria provided
- Record status:
- current
- Accession:
- RCV003760475.1
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
This HGVS expression did not pass validation- 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
Assertion and evidence details
Submission Accession | Submitter | Review Status (Assertion method) | Clinical Significance (Last evaluated) | Origin | Method | Citations |
---|---|---|---|---|---|---|
SCV004540422 | Invitae | criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) | Uncertain significance (Dec 1, 2023) | germline | clinical testing |
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.
- PMID:
- 28492532
- PMCID:
- PMC5632818
Details of each submission
From Invitae, 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: Feb 28, 2024