ClinVar Genomic variation as it relates to human health
NM_000535.7(PMS2):c.2083A>G (p.Ile695Val)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000535.7(PMS2):c.2083A>G (p.Ile695Val)
Variation ID: 2200026 Accession: VCV002200026.3
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 7p22.1 7: 6022546 (GRCh37) [ NCBI UCSC ] 7: 5982915 (GRCh38) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Feb 8, 2023 May 1, 2024 Feb 6, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000535.7:c.2083A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000526.2:p.Ile695Val missense NM_001018040.1:c.1678A>G NP_001018050.1:p.Ile560Val missense NM_001322003.2:c.1678A>G NP_001308932.1:p.Ile560Val missense NM_001322004.2:c.1678A>G NP_001308933.1:p.Ile560Val missense NM_001322005.2:c.1678A>G NP_001308934.1:p.Ile560Val missense NM_001322006.2:c.1927A>G NP_001308935.1:p.Ile643Val missense NM_001322007.2:c.1765A>G NP_001308936.1:p.Ile589Val missense NM_001322008.2:c.1765A>G NP_001308937.1:p.Ile589Val missense NM_001322009.2:c.1678A>G NP_001308938.1:p.Ile560Val missense NM_001322010.2:c.1522A>G NP_001308939.1:p.Ile508Val missense NM_001322011.2:c.1150A>G NP_001308940.1:p.Ile384Val missense NM_001322012.2:c.1150A>G NP_001308941.1:p.Ile384Val missense NM_001322013.2:c.1510A>G NP_001308942.1:p.Ile504Val missense NM_001322014.2:c.2083A>G NP_001308943.1:p.Ile695Val missense NM_001322015.2:c.1774A>G NP_001308944.1:p.Ile592Val missense NM_001406866.1:c.2269A>G NP_001393795.1:p.Ile757Val missense NM_001406868.1:c.2107A>G NP_001393797.1:p.Ile703Val missense NM_001406869.1:c.1975A>G NP_001393798.1:p.Ile659Val missense NM_001406870.1:c.1927A>G NP_001393799.1:p.Ile643Val missense NM_001406871.1:c.2083A>G NP_001393800.1:p.Ile695Val missense NM_001406873.1:c.1885A>G NP_001393802.1:p.Ile629Val missense NM_001406874.1:c.1915A>G NP_001393803.1:p.Ile639Val missense NM_001406875.1:c.1774A>G NP_001393804.1:p.Ile592Val missense NM_001406876.1:c.1765A>G NP_001393805.1:p.Ile589Val missense NM_001406877.1:c.1774A>G NP_001393806.1:p.Ile592Val missense NM_001406878.1:c.1774A>G NP_001393807.1:p.Ile592Val missense NM_001406879.1:c.1774A>G NP_001393808.1:p.Ile592Val missense NM_001406880.1:c.1774A>G NP_001393809.1:p.Ile592Val missense NM_001406881.1:c.1774A>G NP_001393810.1:p.Ile592Val missense NM_001406882.1:c.1774A>G NP_001393811.1:p.Ile592Val missense NM_001406883.1:c.1765A>G NP_001393812.1:p.Ile589Val missense NM_001406884.1:c.1759A>G NP_001393813.1:p.Ile587Val missense NM_001406885.1:c.1747A>G NP_001393814.1:p.Ile583Val missense NM_001406886.1:c.1717A>G NP_001393815.1:p.Ile573Val missense NM_001406887.1:c.1678A>G NP_001393816.1:p.Ile560Val missense NM_001406888.1:c.1678A>G NP_001393817.1:p.Ile560Val missense NM_001406889.1:c.1678A>G NP_001393818.1:p.Ile560Val missense NM_001406890.1:c.1678A>G NP_001393819.1:p.Ile560Val missense NM_001406891.1:c.1678A>G NP_001393820.1:p.Ile560Val missense NM_001406892.1:c.1678A>G NP_001393821.1:p.Ile560Val missense NM_001406893.1:c.1678A>G NP_001393822.1:p.Ile560Val missense NM_001406894.1:c.1678A>G NP_001393823.1:p.Ile560Val missense NM_001406895.1:c.1678A>G NP_001393824.1:p.Ile560Val missense NM_001406896.1:c.1678A>G NP_001393825.1:p.Ile560Val missense NM_001406897.1:c.1678A>G NP_001393826.1:p.Ile560Val missense NM_001406898.1:c.1678A>G NP_001393827.1:p.Ile560Val missense NM_001406899.1:c.1678A>G NP_001393828.1:p.Ile560Val missense NM_001406900.1:c.1618A>G NP_001393829.1:p.Ile540Val missense NM_001406901.1:c.1609A>G NP_001393830.1:p.Ile537Val missense NM_001406902.1:c.1609A>G NP_001393831.1:p.Ile537Val missense NM_001406904.1:c.1570A>G NP_001393833.1:p.Ile524Val missense NM_001406905.1:c.1570A>G NP_001393834.1:p.Ile524Val missense NM_001406906.1:c.1522A>G NP_001393835.1:p.Ile508Val missense NM_001406907.1:c.1522A>G NP_001393836.1:p.Ile508Val missense NM_001406909.1:c.1510A>G NP_001393838.1:p.Ile504Val missense NM_001406911.1:c.1312A>G NP_001393840.1:p.Ile438Val missense NM_001406912.1:c.880A>G NP_001393841.1:p.Ile294Val missense NR_003085.2:n.2165A>G NR_136154.1:n.2170A>G non-coding transcript variant NC_000007.14:g.5982915T>C NC_000007.13:g.6022546T>C NG_008466.1:g.31192A>G LRG_161:g.31192A>G LRG_161t1:c.2083A>G LRG_161p1:p.Ile695Val - Protein change
- I384V, I438V, I560V, I573V, I592V, I643V, I659V, I757V, I508V, I524V, I587V, I695V, I504V, I540V, I583V, I629V, I703V, I294V, I537V, I589V, I639V
- Other names
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- Canonical SPDI
- NC_000007.14:5982914:T:C
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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- Links
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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PMS2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
5232 | 5334 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Uncertain significance (1) |
criteria provided, single submitter
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Sep 24, 2022 | RCV002625264.2 | |
Uncertain significance (1) |
criteria provided, single submitter
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Feb 6, 2024 | RCV004072024.1 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
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The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
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This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Uncertain significance
(Sep 24, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hereditary nonpolyposis colorectal neoplasms
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV003521016.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 14, 2024 |
Comment:
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). … (more)
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. (less)
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Uncertain significance
(Feb 06, 2024)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV005036009.1
First in ClinVar: May 01, 2024 Last updated: May 01, 2024 |
Comment:
The p.I695V variant (also known as c.2083A>G), located in coding exon 12 of the PMS2 gene, results from an A to G substitution at nucleotide … (more)
The p.I695V variant (also known as c.2083A>G), located in coding exon 12 of the PMS2 gene, results from an A to G substitution at nucleotide position 2083. The isoleucine at codon 695 is replaced by valine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear. (less)
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpThere are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for this variant ...
HelpRecord last updated May 08, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.