ClinVar Genomic variation as it relates to human health
NM_000535.7(PMS2):c.2098C>T (p.Gln700Ter)
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.2098C>T (p.Gln700Ter)
Variation ID: 2135280 Accession: VCV002135280.2
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 7p22.1 7: 5982900 (GRCh38) [ NCBI UCSC ] 7: 6022531 (GRCh37) [ 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 Feb 20, 2024 Dec 7, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000535.7:c.2098C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000526.2:p.Gln700Ter nonsense NM_001018040.1:c.1693C>T NP_001018050.1:p.Gln565Ter nonsense NM_001322003.2:c.1693C>T NP_001308932.1:p.Gln565Ter nonsense NM_001322004.2:c.1693C>T NP_001308933.1:p.Gln565Ter nonsense NM_001322005.2:c.1693C>T NP_001308934.1:p.Gln565Ter nonsense NM_001322006.2:c.1942C>T NP_001308935.1:p.Gln648Ter nonsense NM_001322007.2:c.1780C>T NP_001308936.1:p.Gln594Ter nonsense NM_001322008.2:c.1780C>T NP_001308937.1:p.Gln594Ter nonsense NM_001322009.2:c.1693C>T NP_001308938.1:p.Gln565Ter nonsense NM_001322010.2:c.1537C>T NP_001308939.1:p.Gln513Ter nonsense NM_001322011.2:c.1165C>T NP_001308940.1:p.Gln389Ter nonsense NM_001322012.2:c.1165C>T NP_001308941.1:p.Gln389Ter nonsense NM_001322013.2:c.1525C>T NP_001308942.1:p.Gln509Ter nonsense NM_001322014.2:c.2098C>T NP_001308943.1:p.Gln700Ter nonsense NM_001322015.2:c.1789C>T NP_001308944.1:p.Gln597Ter nonsense NM_001406866.1:c.2284C>T NP_001393795.1:p.Gln762Ter nonsense NM_001406868.1:c.2122C>T NP_001393797.1:p.Gln708Ter nonsense NM_001406869.1:c.1990C>T NP_001393798.1:p.Gln664Ter nonsense NM_001406870.1:c.1942C>T NP_001393799.1:p.Gln648Ter nonsense NM_001406871.1:c.2098C>T NP_001393800.1:p.Gln700Ter nonsense NM_001406873.1:c.1900C>T NP_001393802.1:p.Gln634Ter nonsense NM_001406874.1:c.1930C>T NP_001393803.1:p.Gln644Ter nonsense NM_001406875.1:c.1789C>T NP_001393804.1:p.Gln597Ter nonsense NM_001406876.1:c.1780C>T NP_001393805.1:p.Gln594Ter nonsense NM_001406877.1:c.1789C>T NP_001393806.1:p.Gln597Ter nonsense NM_001406878.1:c.1789C>T NP_001393807.1:p.Gln597Ter nonsense NM_001406879.1:c.1789C>T NP_001393808.1:p.Gln597Ter nonsense NM_001406880.1:c.1789C>T NP_001393809.1:p.Gln597Ter nonsense NM_001406881.1:c.1789C>T NP_001393810.1:p.Gln597Ter nonsense NM_001406882.1:c.1789C>T NP_001393811.1:p.Gln597Ter nonsense NM_001406883.1:c.1780C>T NP_001393812.1:p.Gln594Ter nonsense NM_001406884.1:c.1774C>T NP_001393813.1:p.Gln592Ter nonsense NM_001406885.1:c.1762C>T NP_001393814.1:p.Gln588Ter nonsense NM_001406886.1:c.1732C>T NP_001393815.1:p.Gln578Ter nonsense NM_001406887.1:c.1693C>T NP_001393816.1:p.Gln565Ter nonsense NM_001406888.1:c.1693C>T NP_001393817.1:p.Gln565Ter nonsense NM_001406889.1:c.1693C>T NP_001393818.1:p.Gln565Ter nonsense NM_001406890.1:c.1693C>T NP_001393819.1:p.Gln565Ter nonsense NM_001406891.1:c.1693C>T NP_001393820.1:p.Gln565Ter nonsense NM_001406892.1:c.1693C>T NP_001393821.1:p.Gln565Ter nonsense NM_001406893.1:c.1693C>T NP_001393822.1:p.Gln565Ter nonsense NM_001406894.1:c.1693C>T NP_001393823.1:p.Gln565Ter nonsense NM_001406895.1:c.1693C>T NP_001393824.1:p.Gln565Ter nonsense NM_001406896.1:c.1693C>T NP_001393825.1:p.Gln565Ter nonsense NM_001406897.1:c.1693C>T NP_001393826.1:p.Gln565Ter nonsense NM_001406898.1:c.1693C>T NP_001393827.1:p.Gln565Ter nonsense NM_001406899.1:c.1693C>T NP_001393828.1:p.Gln565Ter nonsense NM_001406900.1:c.1633C>T NP_001393829.1:p.Gln545Ter nonsense NM_001406901.1:c.1624C>T NP_001393830.1:p.Gln542Ter nonsense NM_001406902.1:c.1624C>T NP_001393831.1:p.Gln542Ter nonsense NM_001406904.1:c.1585C>T NP_001393833.1:p.Gln529Ter nonsense NM_001406905.1:c.1585C>T NP_001393834.1:p.Gln529Ter nonsense NM_001406906.1:c.1537C>T NP_001393835.1:p.Gln513Ter nonsense NM_001406907.1:c.1537C>T NP_001393836.1:p.Gln513Ter nonsense NM_001406909.1:c.1525C>T NP_001393838.1:p.Gln509Ter nonsense NM_001406911.1:c.1327C>T NP_001393840.1:p.Gln443Ter nonsense NM_001406912.1:c.895C>T NP_001393841.1:p.Gln299Ter nonsense NR_003085.2:n.2180C>T NR_136154.1:n.2185C>T non-coding transcript variant NC_000007.14:g.5982900G>A NC_000007.13:g.6022531G>A NG_008466.1:g.31207C>T LRG_161:g.31207C>T LRG_161t1:c.2098C>T LRG_161p1:p.Gln700Ter - Protein change
- Q443*, Q509*, Q529*, Q578*, Q597*, Q700*, Q762*, Q588*, Q592*, Q594*, Q664*, Q299*, Q644*, Q648*, Q708*, Q389*, Q513*, Q542*, Q545*, Q565*, Q634*
- Other names
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- Canonical SPDI
- NC_000007.14:5982899:G:A
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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
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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
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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
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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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Pathogenic (1) |
criteria provided, single submitter
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Dec 7, 2023 | RCV003066212.2 |
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
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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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Pathogenic
(Dec 07, 2023)
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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: SCV003353017.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Gln700*) in the PMS2 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Gln700*) in the PMS2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PMS2 are known to be pathogenic (PMID: 21376568, 24362816). 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. ClinVar contains an entry for this variant (Variation ID: 2135280). For these reasons, this variant has been classified as Pathogenic. (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
HelpTitle | Author | Journal | Year | Link |
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Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database. | Thompson BA | Nature genetics | 2014 | PMID: 24362816 |
Paediatric intestinal cancer and polyposis due to bi-allelic PMS2 mutations: case series, review and follow-up guidelines. | Herkert JC | European journal of cancer (Oxford, England : 1990) | 2011 | PMID: 21376568 |
Text-mined citations for this variant ...
HelpRecord last updated Feb 29, 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.