This change (c.1903G>T) replaces the codon for glutamate with a termination codon. This causes the protein to be truncated at exon 11. This variant is not listed in the population database gnomAD or ClinVar. Therefore, we classify this variant as likely pathogenic.
ClinVar Genomic variation as it relates to human health
NM_000535.7(PMS2):c.1903G>T (p.Glu635Ter)
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.
Pathogenic
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.1903G>T (p.Glu635Ter)
Variation ID: 2573186 Accession: VCV002573186.1
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 7p22.1 7: 5986862 (GRCh38) [ NCBI UCSC ] 7: 6026493 (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 Jul 29, 2023 Jul 29, 2023 Jul 7, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000535.7:c.1903G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000526.2:p.Glu635Ter nonsense NM_001018040.1:c.1498G>T NP_001018050.1:p.Glu500Ter nonsense NM_001322003.2:c.1498G>T NP_001308932.1:p.Glu500Ter nonsense NM_001322004.2:c.1498G>T NP_001308933.1:p.Glu500Ter nonsense NM_001322005.2:c.1498G>T NP_001308934.1:p.Glu500Ter nonsense NM_001322006.2:c.1747G>T NP_001308935.1:p.Glu583Ter nonsense NM_001322007.2:c.1585G>T NP_001308936.1:p.Glu529Ter nonsense NM_001322008.2:c.1585G>T NP_001308937.1:p.Glu529Ter nonsense NM_001322009.2:c.1498G>T NP_001308938.1:p.Glu500Ter nonsense NM_001322010.2:c.1342G>T NP_001308939.1:p.Glu448Ter nonsense NM_001322011.2:c.970G>T NP_001308940.1:p.Glu324Ter nonsense NM_001322012.2:c.970G>T NP_001308941.1:p.Glu324Ter nonsense NM_001322013.2:c.1330G>T NP_001308942.1:p.Glu444Ter nonsense NM_001322014.2:c.1903G>T NP_001308943.1:p.Glu635Ter nonsense NM_001322015.2:c.1594G>T NP_001308944.1:p.Glu532Ter nonsense NM_001406866.1:c.2089G>T NP_001393795.1:p.Glu697Ter nonsense NM_001406868.1:c.1927G>T NP_001393797.1:p.Glu643Ter nonsense NM_001406869.1:c.1795G>T NP_001393798.1:p.Glu599Ter nonsense NM_001406870.1:c.1747G>T NP_001393799.1:p.Glu583Ter nonsense NM_001406871.1:c.1903G>T NP_001393800.1:p.Glu635Ter nonsense NM_001406872.1:c.1903G>T NP_001393801.1:p.Glu635Ter nonsense NM_001406873.1:c.1705G>T NP_001393802.1:p.Glu569Ter nonsense NM_001406874.1:c.1735G>T NP_001393803.1:p.Glu579Ter nonsense NM_001406875.1:c.1594G>T NP_001393804.1:p.Glu532Ter nonsense NM_001406876.1:c.1585G>T NP_001393805.1:p.Glu529Ter nonsense NM_001406877.1:c.1594G>T NP_001393806.1:p.Glu532Ter nonsense NM_001406878.1:c.1594G>T NP_001393807.1:p.Glu532Ter nonsense NM_001406879.1:c.1594G>T NP_001393808.1:p.Glu532Ter nonsense NM_001406880.1:c.1594G>T NP_001393809.1:p.Glu532Ter nonsense NM_001406881.1:c.1594G>T NP_001393810.1:p.Glu532Ter nonsense NM_001406882.1:c.1594G>T NP_001393811.1:p.Glu532Ter nonsense NM_001406883.1:c.1585G>T NP_001393812.1:p.Glu529Ter nonsense NM_001406884.1:c.1579G>T NP_001393813.1:p.Glu527Ter nonsense NM_001406885.1:c.1567G>T NP_001393814.1:p.Glu523Ter nonsense NM_001406886.1:c.1537G>T NP_001393815.1:p.Glu513Ter nonsense NM_001406887.1:c.1498G>T NP_001393816.1:p.Glu500Ter nonsense NM_001406888.1:c.1498G>T NP_001393817.1:p.Glu500Ter nonsense NM_001406889.1:c.1498G>T NP_001393818.1:p.Glu500Ter nonsense NM_001406890.1:c.1498G>T NP_001393819.1:p.Glu500Ter nonsense NM_001406891.1:c.1498G>T NP_001393820.1:p.Glu500Ter nonsense NM_001406892.1:c.1498G>T NP_001393821.1:p.Glu500Ter nonsense NM_001406893.1:c.1498G>T NP_001393822.1:p.Glu500Ter nonsense NM_001406894.1:c.1498G>T NP_001393823.1:p.Glu500Ter nonsense NM_001406895.1:c.1498G>T NP_001393824.1:p.Glu500Ter nonsense NM_001406896.1:c.1498G>T NP_001393825.1:p.Glu500Ter nonsense NM_001406897.1:c.1498G>T NP_001393826.1:p.Glu500Ter nonsense NM_001406898.1:c.1498G>T NP_001393827.1:p.Glu500Ter nonsense NM_001406899.1:c.1498G>T NP_001393828.1:p.Glu500Ter nonsense NM_001406900.1:c.1438G>T NP_001393829.1:p.Glu480Ter nonsense NM_001406901.1:c.1429G>T NP_001393830.1:p.Glu477Ter nonsense NM_001406902.1:c.1429G>T NP_001393831.1:p.Glu477Ter nonsense NM_001406903.1:c.1585G>T NP_001393832.1:p.Glu529Ter nonsense NM_001406904.1:c.1390G>T NP_001393833.1:p.Glu464Ter nonsense NM_001406905.1:c.1390G>T NP_001393834.1:p.Glu464Ter nonsense NM_001406906.1:c.1342G>T NP_001393835.1:p.Glu448Ter nonsense NM_001406907.1:c.1342G>T NP_001393836.1:p.Glu448Ter nonsense NM_001406908.1:c.1498G>T NP_001393837.1:p.Glu500Ter nonsense NM_001406909.1:c.1330G>T NP_001393838.1:p.Glu444Ter nonsense NM_001406910.1:c.1498G>T NP_001393839.1:p.Glu500Ter nonsense NM_001406911.1:c.1132G>T NP_001393840.1:p.Glu378Ter nonsense NM_001406912.1:c.804-3871G>T intron variant NR_003085.2:n.1985G>T NR_136154.1:n.1990G>T non-coding transcript variant NC_000007.14:g.5986862C>A NC_000007.13:g.6026493C>A NG_008466.1:g.27245G>T LRG_161:g.27245G>T LRG_161t1:c.1903G>T LRG_161p1:p.Glu635Ter - Protein change
- E324*, E378*, E444*, E448*, E464*, E477*, E480*, E500*, E513*, E523*, E527*, E529*, E532*, E569*, E579*, E583*, E599*, E635*, E643*, E697*
- Other names
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- Canonical SPDI
- NC_000007.14:5986861:C: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
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 | ||
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| 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 |
5242 | 5344 | |
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. |
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| Pathogenic (1) |
criteria provided, single submitter
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Jul 7, 2023 | RCV003315491.1 |
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
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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Pathogenic
(Jul 07, 2023)
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criteria provided, single submitter
Method: clinical testing
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Mismatch repair cancer syndrome 4
Affected status: yes
Allele origin:
unknown
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KCCC/NGS Laboratory, Kuwait Cancer Control Center
Accession: SCV004015234.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023 |
Comment:
This change (c.1903G>T) replaces the codon for glutamate with a termination codon. This causes the protein to be truncated at exon 11. This variant is … (more)
This change (c.1903G>T) replaces the codon for glutamate with a termination codon. This causes the protein to be truncated at exon 11. This variant is not listed in the population database gnomAD or ClinVar. Therefore, we classify this variant as likely pathogenic. (less)
|
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 change (c.1903G>T) replaces the codon for glutamate with a termination codon. This causes the protein to be truncated at exon 11. This variant is not listed in the population database gnomAD or ClinVar. Therefore, we classify this variant as likely pathogenic.
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 Jul 29, 2023
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.