This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
ClinVar Genomic variation as it relates to human health
NM_000535.7(PMS2):c.51_55del (p.Ile18fs)
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.
(6)
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
6
criteria provided, multiple submitters, no conflicts
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.51_55del (p.Ile18fs)
Variation ID: 1745351 Accession: VCV001745351.24
- Type and length
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Deletion, 5 bp
- Location
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Cytogenetic: 7p22.1 7: 6006000-6006004 (GRCh38) [ NCBI UCSC ] 7: 6045631-6045635 (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 Nov 29, 2022 May 1, 2024 Jan 23, 2024 - HGVS
- ... more HGVS ... less HGVS
- Protein change
- I18fs
- Other names
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- Canonical SPDI
- NC_000007.14:6005999:CAATA:
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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 |
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. |
|---|---|---|---|---|
| Pathogenic (1) |
criteria provided, single submitter
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Sep 21, 2016 | RCV002335996.3 | |
| Pathogenic (1) |
no assertion criteria provided
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Jul 1, 2021 | RCV003164536.2 | |
| Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Sep 18, 2023 | RCV003454163.2 | |
| Pathogenic (1) |
criteria provided, single submitter
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Apr 24, 2023 | RCV003759135.2 | |
| Pathogenic (1) |
criteria provided, single submitter
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Jan 23, 2024 | RCV003988000.1 |
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
(Sep 18, 2023)
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criteria provided, single submitter
Method: clinical testing
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Lynch syndrome 4
Affected status: unknown
Allele origin:
unknown
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Myriad Genetics, Inc.
Accession: SCV004188636.1
First in ClinVar: Dec 24, 2023 Last updated: Dec 24, 2023 |
Comment:
This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
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Pathogenic
(Jul 03, 2022)
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criteria provided, single submitter
Method: clinical testing
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Lynch syndrome 4
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004207892.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Apr 24, 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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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV004540444.1
First in ClinVar: Feb 20, 2024 Last updated: Feb 20, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1745351). This premature translational stop signal … (more)
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1745351). This premature translational stop signal has been observed in individual(s) with peritoneal cancer (PMID: 29348823). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ile18Serfs*34) 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). (less)
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Pathogenic
(Jan 23, 2024)
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criteria provided, single submitter
Method: clinical testing
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Hereditary nonpolyposis colon cancer
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV004803684.1
First in ClinVar: Mar 30, 2024 Last updated: Mar 30, 2024 |
Comment:
Variant summary: PMS2 c.51_55delTATTG (p.Ile18SerfsX34) results in a premature termination codon, predicted to cause absence of the protein due to nonsense mediated decay, which is … (more)
Variant summary: PMS2 c.51_55delTATTG (p.Ile18SerfsX34) results in a premature termination codon, predicted to cause absence of the protein due to nonsense mediated decay, which is a commonly known mechanism for disease. The variant was absent in 245594 control chromosomes (gnomAD). c.51_55delTATTG has been reported in the literature in an individual(s) affected with Hereditary Nonpolyposis Colorectal Cancer (Nakamura_2023). The following publication has been ascertained in the context of this evaluation (PMID: 36999887). ClinVar contains an entry for this variant (Variation ID: 1745351). Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Sep 21, 2016)
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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: SCV002641940.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The c.51_55delTATTG pathogenic mutation, located in coding exon 2 of the PMS2 gene, results from a deletion of 5 nucleotides at nucleotide positions 51 to … (more)
The c.51_55delTATTG pathogenic mutation, located in coding exon 2 of the PMS2 gene, results from a deletion of 5 nucleotides at nucleotide positions 51 to 55, causing a translational frameshift with a predicted alternate stop codon. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (less)
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Pathogenic
(Jul 01, 2021)
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no assertion criteria provided
Method: research
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Gastric cancer
Affected status: unknown
Allele origin:
germline
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Laboratory for Genotyping Development, RIKEN
Accession: SCV002758381.1
First in ClinVar: Apr 15, 2023 Last updated: Apr 15, 2023 |
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Comment:
Comment:
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1745351). This premature translational stop signal has been observed in individual(s) with peritoneal cancer (PMID: 29348823). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ile18Serfs*34) 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).
Comment:
Variant summary: PMS2 c.51_55delTATTG (p.Ile18SerfsX34) results in a premature termination codon, predicted to cause absence of the protein due to nonsense mediated decay, which is a commonly known mechanism for disease. The variant was absent in 245594 control chromosomes (gnomAD). c.51_55delTATTG has been reported in the literature in an individual(s) affected with Hereditary Nonpolyposis Colorectal Cancer (Nakamura_2023). The following publication has been ascertained in the context of this evaluation (PMID: 36999887). ClinVar contains an entry for this variant (Variation ID: 1745351). Based on the evidence outlined above, the variant was classified as pathogenic.
Comment:
The c.51_55delTATTG pathogenic mutation, located in coding exon 2 of the PMS2 gene, results from a deletion of 5 nucleotides at nucleotide positions 51 to 55, causing a translational frameshift with a predicted alternate stop codon. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
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 variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
Comment:
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1745351). This premature translational stop signal has been observed in individual(s) with peritoneal cancer (PMID: 29348823). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ile18Serfs*34) 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).
Comment:
Variant summary: PMS2 c.51_55delTATTG (p.Ile18SerfsX34) results in a premature termination codon, predicted to cause absence of the protein due to nonsense mediated decay, which is a commonly known mechanism for disease. The variant was absent in 245594 control chromosomes (gnomAD). c.51_55delTATTG has been reported in the literature in an individual(s) affected with Hereditary Nonpolyposis Colorectal Cancer (Nakamura_2023). The following publication has been ascertained in the context of this evaluation (PMID: 36999887). ClinVar contains an entry for this variant (Variation ID: 1745351). Based on the evidence outlined above, the variant was classified as pathogenic.
Comment:
The c.51_55delTATTG pathogenic mutation, located in coding exon 2 of the PMS2 gene, results from a deletion of 5 nucleotides at nucleotide positions 51 to 55, causing a translational frameshift with a predicted alternate stop codon. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Molecular genetic positioning of small intestine and papilla of Vater carcinomas including clinicopathological classification. | Nakamura M | Cancer medicine | 2023 | PMID: 36999887 |
| Helicobacter pylori, Homologous-Recombination Genes, and Gastric Cancer. | Usui Y | The New England journal of medicine | 2023 | PMID: 36988593 |
| Prevalence of pathogenic germline variants detected by multigene sequencing in unselected Japanese patients with ovarian cancer. | Hirasawa A | Oncotarget | 2017 | PMID: 29348823 |
| 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 Sep 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.