This missense variant replaces valine with alanine at codon 367 of the PMS2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with PMS2-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
ClinVar Genomic variation as it relates to human health
NM_000535.7(PMS2):c.1100T>C (p.Val367Ala)
Germline
Classification
Help
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.
(1)
Help
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.
Uncertain significance
1
criteria provided, single submitter
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000535.7(PMS2):c.1100T>C (p.Val367Ala)
Variation ID: 3072453 Accession: VCV003072453.1
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 7p22.1 7: 5989844 (GRCh38) [ NCBI UCSC ] 7: 6029475 (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 Apr 20, 2024 Apr 20, 2024 Jul 19, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000535.7:c.1100T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000526.2:p.Val367Ala missense NM_001018040.1:c.695T>C NP_001018050.1:p.Val232Ala missense NM_001322003.2:c.695T>C NP_001308932.1:p.Val232Ala missense NM_001322004.2:c.695T>C NP_001308933.1:p.Val232Ala missense NM_001322005.2:c.695T>C NP_001308934.1:p.Val232Ala missense NM_001322006.2:c.988+2129T>C intron variant NM_001322007.2:c.782T>C NP_001308936.1:p.Val261Ala missense NM_001322008.2:c.782T>C NP_001308937.1:p.Val261Ala missense NM_001322009.2:c.695T>C NP_001308938.1:p.Val232Ala missense NM_001322010.2:c.583+2129T>C intron variant NM_001322011.2:c.167T>C NP_001308940.1:p.Val56Ala missense NM_001322012.2:c.167T>C NP_001308941.1:p.Val56Ala missense NM_001322013.2:c.527T>C NP_001308942.1:p.Val176Ala missense NM_001322014.2:c.1100T>C NP_001308943.1:p.Val367Ala missense NM_001322015.2:c.791T>C NP_001308944.1:p.Val264Ala missense NM_001406866.1:c.1286T>C NP_001393795.1:p.Val429Ala missense NM_001406868.1:c.1124T>C NP_001393797.1:p.Val375Ala missense NM_001406869.1:c.992T>C NP_001393798.1:p.Val331Ala missense NM_001406870.1:c.988+2129T>C intron variant NM_001406871.1:c.1100T>C NP_001393800.1:p.Val367Ala missense NM_001406872.1:c.1100T>C NP_001393801.1:p.Val367Ala missense NM_001406873.1:c.902T>C NP_001393802.1:p.Val301Ala missense NM_001406874.1:c.932T>C NP_001393803.1:p.Val311Ala missense NM_001406875.1:c.791T>C NP_001393804.1:p.Val264Ala missense NM_001406876.1:c.782T>C NP_001393805.1:p.Val261Ala missense NM_001406877.1:c.791T>C NP_001393806.1:p.Val264Ala missense NM_001406878.1:c.791T>C NP_001393807.1:p.Val264Ala missense NM_001406879.1:c.791T>C NP_001393808.1:p.Val264Ala missense NM_001406880.1:c.791T>C NP_001393809.1:p.Val264Ala missense NM_001406881.1:c.791T>C NP_001393810.1:p.Val264Ala missense NM_001406882.1:c.791T>C NP_001393811.1:p.Val264Ala missense NM_001406883.1:c.782T>C NP_001393812.1:p.Val261Ala missense NM_001406884.1:c.820+2129T>C intron variant NM_001406885.1:c.764T>C NP_001393814.1:p.Val255Ala missense NM_001406886.1:c.734T>C NP_001393815.1:p.Val245Ala missense NM_001406887.1:c.695T>C NP_001393816.1:p.Val232Ala missense NM_001406888.1:c.695T>C NP_001393817.1:p.Val232Ala missense NM_001406889.1:c.695T>C NP_001393818.1:p.Val232Ala missense NM_001406890.1:c.695T>C NP_001393819.1:p.Val232Ala missense NM_001406891.1:c.695T>C NP_001393820.1:p.Val232Ala missense NM_001406892.1:c.695T>C NP_001393821.1:p.Val232Ala missense NM_001406893.1:c.695T>C NP_001393822.1:p.Val232Ala missense NM_001406894.1:c.695T>C NP_001393823.1:p.Val232Ala missense NM_001406895.1:c.695T>C NP_001393824.1:p.Val232Ala missense NM_001406896.1:c.695T>C NP_001393825.1:p.Val232Ala missense NM_001406897.1:c.695T>C NP_001393826.1:p.Val232Ala missense NM_001406898.1:c.695T>C NP_001393827.1:p.Val232Ala missense NM_001406899.1:c.695T>C NP_001393828.1:p.Val232Ala missense NM_001406900.1:c.679+2129T>C intron variant NM_001406901.1:c.670+2129T>C intron variant NM_001406902.1:c.670+2129T>C intron variant NM_001406903.1:c.782T>C NP_001393832.1:p.Val261Ala missense NM_001406904.1:c.587T>C NP_001393833.1:p.Val196Ala missense NM_001406905.1:c.587T>C NP_001393834.1:p.Val196Ala missense NM_001406906.1:c.583+2129T>C intron variant NM_001406907.1:c.583+2129T>C intron variant NM_001406908.1:c.695T>C NP_001393837.1:p.Val232Ala missense NM_001406909.1:c.527T>C NP_001393838.1:p.Val176Ala missense NM_001406910.1:c.695T>C NP_001393839.1:p.Val232Ala missense NM_001406911.1:c.329T>C NP_001393840.1:p.Val110Ala missense NM_001406912.1:c.804-6853T>C intron variant NR_003085.2:n.1182T>C NR_136154.1:n.1187T>C non-coding transcript variant NC_000007.14:g.5989844A>G NC_000007.13:g.6029475A>G NG_008466.1:g.24263T>C LRG_161:g.24263T>C LRG_161t1:c.1100T>C LRG_161p1:p.Val367Ala - Protein change
- V110A, V176A, V196A, V232A, V245A, V255A, V261A, V264A, V301A, V311A, V331A, V367A, V375A, V429A, V56A
- Other names
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- Canonical SPDI
- NC_000007.14:5989843:A:G
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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
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
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
Help
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 |
5241 | 5343 | |
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
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Uncertain significance (1) |
criteria provided, single submitter
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Jul 19, 2023 | RCV004013475.2 |
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
Help
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
Help
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
(Jul 19, 2023)
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criteria provided, single submitter
Method: clinical testing
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Lynch syndrome
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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All of Us Research Program, National Institutes of Health
Accession: SCV004834040.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
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Comment:
This missense variant replaces valine with alanine at codon 367 of the PMS2 protein. Computational prediction suggests that this variant may not impact protein structure … (more)
This missense variant replaces valine with alanine at codon 367 of the PMS2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with PMS2-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. (less)
Number of individuals with the variant: 1
|
Comment:
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. |
Comment:
This missense variant replaces valine with alanine at codon 367 of the PMS2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with PMS2-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Citations for germline classification of this variant
Help| There 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.