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.503dup (p.Arg169fs)
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.
(3)
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/Likely pathogenic
3
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000535.7(PMS2):c.503dup (p.Arg169fs)
Variation ID: 2674264 Accession: VCV002674264.3
- Type and length
-
Duplication, 1 bp
- Location
-
Cytogenetic: 7p22.1 7: 6002486-6002487 (GRCh38) [ NCBI UCSC ] 7: 6042117-6042118 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Dec 25, 2023 Jun 17, 2024 Jan 5, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000535.7:c.503dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000526.2:p.Arg169fs frameshift NM_001018040.1:c.98dup NP_001018050.1:p.Arg34Alafs frameshift NM_001322003.2:c.98dup NP_001308932.1:p.Arg34fs frameshift NM_001322004.2:c.98dup NP_001308933.1:p.Arg34fs frameshift NM_001322005.2:c.98dup NP_001308934.1:p.Arg34fs frameshift NM_001322006.2:c.503dup NP_001308935.1:p.Arg169fs frameshift NM_001322007.2:c.185dup NP_001308936.1:p.Arg63fs frameshift NM_001322008.2:c.185dup NP_001308937.1:p.Arg63fs frameshift NM_001322009.2:c.98dup NP_001308938.1:p.Arg34fs frameshift NM_001322010.2:c.98dup NP_001308939.1:p.Arg34fs frameshift NM_001322011.2:c.-382dup 5 prime UTR NM_001322012.2:c.-382dup 5 prime UTR NM_001322013.2:c.98dup NP_001308942.1:p.Arg34fs frameshift NM_001322014.2:c.503dup NP_001308943.1:p.Arg169fs frameshift NM_001322015.2:c.194dup NP_001308944.1:p.Arg66fs frameshift NM_001406866.1:c.689dup NP_001393795.1:p.Arg231fs frameshift NM_001406868.1:c.527dup NP_001393797.1:p.Arg177fs frameshift NM_001406869.1:c.503dup NP_001393798.1:p.Arg169fs frameshift NM_001406870.1:c.503dup NP_001393799.1:p.Arg169fs frameshift NM_001406871.1:c.503dup NP_001393800.1:p.Arg169fs frameshift NM_001406872.1:c.503dup NP_001393801.1:p.Arg169fs frameshift NM_001406873.1:c.503dup NP_001393802.1:p.Arg169fs frameshift NM_001406874.1:c.503dup NP_001393803.1:p.Arg169fs frameshift NM_001406875.1:c.194dup NP_001393804.1:p.Arg66fs frameshift NM_001406876.1:c.185dup NP_001393805.1:p.Arg63fs frameshift NM_001406877.1:c.194dup NP_001393806.1:p.Arg66fs frameshift NM_001406878.1:c.194dup NP_001393807.1:p.Arg66fs frameshift NM_001406879.1:c.194dup NP_001393808.1:p.Arg66fs frameshift NM_001406880.1:c.194dup NP_001393809.1:p.Arg66fs frameshift NM_001406881.1:c.194dup NP_001393810.1:p.Arg66fs frameshift NM_001406882.1:c.194dup NP_001393811.1:p.Arg66fs frameshift NM_001406883.1:c.185dup NP_001393812.1:p.Arg63fs frameshift NM_001406884.1:c.503dup NP_001393813.1:p.Arg169fs frameshift NM_001406885.1:c.250+1485dup intron variant NM_001406886.1:c.503dup NP_001393815.1:p.Arg169fs frameshift NM_001406887.1:c.98dup NP_001393816.1:p.Arg34fs frameshift NM_001406888.1:c.98dup NP_001393817.1:p.Arg34fs frameshift NM_001406889.1:c.98dup NP_001393818.1:p.Arg34fs frameshift NM_001406890.1:c.98dup NP_001393819.1:p.Arg34fs frameshift NM_001406891.1:c.98dup NP_001393820.1:p.Arg34fs frameshift NM_001406892.1:c.98dup NP_001393821.1:p.Arg34fs frameshift NM_001406893.1:c.98dup NP_001393822.1:p.Arg34fs frameshift NM_001406894.1:c.98dup NP_001393823.1:p.Arg34fs frameshift NM_001406895.1:c.98dup NP_001393824.1:p.Arg34fs frameshift NM_001406896.1:c.98dup NP_001393825.1:p.Arg34fs frameshift NM_001406897.1:c.98dup NP_001393826.1:p.Arg34fs frameshift NM_001406898.1:c.98dup NP_001393827.1:p.Arg34fs frameshift NM_001406899.1:c.98dup NP_001393828.1:p.Arg34fs frameshift NM_001406900.1:c.194dup NP_001393829.1:p.Arg66fs frameshift NM_001406901.1:c.185dup NP_001393830.1:p.Arg63fs frameshift NM_001406902.1:c.185dup NP_001393831.1:p.Arg63fs frameshift NM_001406903.1:c.185dup NP_001393832.1:p.Arg63fs frameshift NM_001406904.1:c.98dup NP_001393833.1:p.Arg34fs frameshift NM_001406905.1:c.98dup NP_001393834.1:p.Arg34fs frameshift NM_001406906.1:c.98dup NP_001393835.1:p.Arg34fs frameshift NM_001406907.1:c.98dup NP_001393836.1:p.Arg34fs frameshift NM_001406908.1:c.98dup NP_001393837.1:p.Arg34fs frameshift NM_001406909.1:c.98dup NP_001393838.1:p.Arg34fs frameshift NM_001406910.1:c.98dup NP_001393839.1:p.Arg34fs frameshift NM_001406911.1:c.98dup NP_001393840.1:p.Arg34fs frameshift NM_001406912.1:c.503dup NP_001393841.1:p.Arg169fs frameshift NR_003085.2:n.585dup NR_136154.1:n.590dup non-coding transcript variant NC_000007.14:g.6002487dup NC_000007.13:g.6042118dup NG_008466.1:g.11620dup LRG_161:g.11620dup LRG_161t1:c.503dup LRG_161p1:p.Arg169Alafs - Protein change
- R169fs, R177fs, R231fs, R34fs, R63fs, R66fs
- Other names
- -
- Canonical SPDI
- NC_000007.14:6002486:A:AA
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
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.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
- -
- 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. |
|||
| 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/Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Jan 5, 2024 | RCV003452460.2 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Jun 9, 2023 | RCV003759865.2 |
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. |
|
|---|---|---|---|---|---|
|
Pathogenic
(Sep 18, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Lynch syndrome 4
Affected status: unknown
Allele origin:
unknown
|
Myriad Genetics, Inc.
Accession: SCV004188696.1
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.
|
|
|
Pathogenic
(Jun 09, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary nonpolyposis colorectal neoplasms
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV004433387.1
First in ClinVar: Feb 20, 2024 Last updated: Feb 20, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with PMS2-related conditions. … (more)
For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with PMS2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg169Alafs*3) 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)
|
|
|
Likely pathogenic
(Jan 05, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Lynch syndrome 4
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV005056464.1
First in ClinVar: Jun 17, 2024 Last updated: Jun 17, 2024 |
|
Comment:
Comment:
For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with PMS2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg169Alafs*3) 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).
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. This variant has not been reported in the literature in individuals affected with PMS2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg169Alafs*3) 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).
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| 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 30, 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.