The c.2026_2027delAT pathogenic mutation, located in coding exon 12 of the PMS2 gene, results from a deletion of two nucleotides at nucleotide positions 2026 to 2027, causing a translational frameshift with a predicted alternate stop codon (p.M676Gfs*7). 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.
ClinVar Genomic variation as it relates to human health
NM_000535.7(PMS2):c.2026_2027del (p.Met676fs)
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)
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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.2026_2027del (p.Met676fs)
Variation ID: 1784648 Accession: VCV001784648.2
- Type and length
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Deletion, 2 bp
- Location
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Cytogenetic: 7p22.1 7: 5982971-5982972 (GRCh38) [ NCBI UCSC ] 7: 6022602-6022603 (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 Mar 3, 2021 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000535.7:c.2026_2027del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000526.2:p.Met676fs frameshift NM_001018040.1:c.1621_1622delAT NP_001018050.1:p.Met541Glyfs frameshift NM_001322003.2:c.1621_1622del NP_001308932.1:p.Met541fs frameshift NM_001322004.2:c.1621_1622del NP_001308933.1:p.Met541fs frameshift NM_001322005.2:c.1621_1622del NP_001308934.1:p.Met541fs frameshift NM_001322006.2:c.1870_1871del NP_001308935.1:p.Met624fs frameshift NM_001322007.2:c.1708_1709del NP_001308936.1:p.Met570fs frameshift NM_001322008.2:c.1708_1709del NP_001308937.1:p.Met570fs frameshift NM_001322009.2:c.1621_1622del NP_001308938.1:p.Met541fs frameshift NM_001322010.2:c.1465_1466del NP_001308939.1:p.Met489fs frameshift NM_001322011.2:c.1093_1094del NP_001308940.1:p.Met365fs frameshift NM_001322012.2:c.1093_1094del NP_001308941.1:p.Met365fs frameshift NM_001322013.2:c.1453_1454del NP_001308942.1:p.Met485fs frameshift NM_001322014.2:c.2026_2027del NP_001308943.1:p.Met676fs frameshift NM_001322015.2:c.1717_1718del NP_001308944.1:p.Met573fs frameshift NM_001406866.1:c.2212_2213delAT NP_001393795.1:p.Met738Glyfs frameshift NM_001406868.1:c.2050_2051delAT NP_001393797.1:p.Met684Glyfs frameshift NM_001406869.1:c.1918_1919delAT NP_001393798.1:p.Met640Glyfs frameshift NM_001406870.1:c.1870_1871delAT NP_001393799.1:p.Met624Glyfs frameshift NM_001406871.1:c.2026_2027delAT NP_001393800.1:p.Met676Glyfs frameshift NM_001406873.1:c.1828_1829delAT NP_001393802.1:p.Met610Glyfs frameshift NM_001406874.1:c.1858_1859delAT NP_001393803.1:p.Met620Glyfs frameshift NM_001406875.1:c.1717_1718delAT NP_001393804.1:p.Met573Glyfs frameshift NM_001406876.1:c.1708_1709delAT NP_001393805.1:p.Met570Glyfs frameshift NM_001406877.1:c.1717_1718delAT NP_001393806.1:p.Met573Glyfs frameshift NM_001406878.1:c.1717_1718delAT NP_001393807.1:p.Met573Glyfs frameshift NM_001406879.1:c.1717_1718delAT NP_001393808.1:p.Met573Glyfs frameshift NM_001406880.1:c.1717_1718delAT NP_001393809.1:p.Met573Glyfs frameshift NM_001406881.1:c.1717_1718delAT NP_001393810.1:p.Met573Glyfs frameshift NM_001406882.1:c.1717_1718delAT NP_001393811.1:p.Met573Glyfs frameshift NM_001406883.1:c.1708_1709delAT NP_001393812.1:p.Met570Glyfs frameshift NM_001406884.1:c.1702_1703delAT NP_001393813.1:p.Met568Glyfs frameshift NM_001406885.1:c.1690_1691delAT NP_001393814.1:p.Met564Glyfs frameshift NM_001406886.1:c.1660_1661delAT NP_001393815.1:p.Met554Glyfs frameshift NM_001406887.1:c.1621_1622delAT NP_001393816.1:p.Met541Glyfs frameshift NM_001406888.1:c.1621_1622delAT NP_001393817.1:p.Met541Glyfs frameshift NM_001406889.1:c.1621_1622delAT NP_001393818.1:p.Met541Glyfs frameshift NM_001406890.1:c.1621_1622delAT NP_001393819.1:p.Met541Glyfs frameshift NM_001406891.1:c.1621_1622delAT NP_001393820.1:p.Met541Glyfs frameshift NM_001406892.1:c.1621_1622delAT NP_001393821.1:p.Met541Glyfs frameshift NM_001406893.1:c.1621_1622delAT NP_001393822.1:p.Met541Glyfs frameshift NM_001406894.1:c.1621_1622delAT NP_001393823.1:p.Met541Glyfs frameshift NM_001406895.1:c.1621_1622delAT NP_001393824.1:p.Met541Glyfs frameshift NM_001406896.1:c.1621_1622delAT NP_001393825.1:p.Met541Glyfs frameshift NM_001406897.1:c.1621_1622delAT NP_001393826.1:p.Met541Glyfs frameshift NM_001406898.1:c.1621_1622delAT NP_001393827.1:p.Met541Glyfs frameshift NM_001406899.1:c.1621_1622delAT NP_001393828.1:p.Met541Glyfs frameshift NM_001406900.1:c.1561_1562delAT NP_001393829.1:p.Met521Glyfs frameshift NM_001406901.1:c.1552_1553delAT NP_001393830.1:p.Met518Glyfs frameshift NM_001406902.1:c.1552_1553delAT NP_001393831.1:p.Met518Glyfs frameshift NM_001406904.1:c.1513_1514delAT NP_001393833.1:p.Met505Glyfs frameshift NM_001406905.1:c.1513_1514delAT NP_001393834.1:p.Met505Glyfs frameshift NM_001406906.1:c.1465_1466delAT NP_001393835.1:p.Met489Glyfs frameshift NM_001406907.1:c.1465_1466delAT NP_001393836.1:p.Met489Glyfs frameshift NM_001406909.1:c.1453_1454delAT NP_001393838.1:p.Met485Glyfs frameshift NM_001406911.1:c.1255_1256delAT NP_001393840.1:p.Met419Glyfs frameshift NM_001406912.1:c.823_824delAT NP_001393841.1:p.Met275Glyfs frameshift NR_003085.2:n.2108_2109delAT NR_136154.1:n.2113_2114del non-coding transcript variant NC_000007.14:g.5982971_5982972del NC_000007.13:g.6022602_6022603del NG_008466.1:g.31135_31136del LRG_161:g.31135_31136del LRG_161t1:c.2026_2027del LRG_161p1:p.Met676Glyfs - Protein change
- M570fs, M573fs, M624fs, M365fs, M541fs, M485fs, M489fs, M676fs
- Other names
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- Canonical SPDI
- NC_000007.14:5982970:AT:
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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. |
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| Pathogenic (1) |
criteria provided, single submitter
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Mar 3, 2021 | RCV002419677.2 |
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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Pathogenic
(Mar 03, 2021)
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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: SCV002718635.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The c.2026_2027delAT pathogenic mutation, located in coding exon 12 of the PMS2 gene, results from a deletion of two nucleotides at nucleotide positions 2026 to … (more)
The c.2026_2027delAT pathogenic mutation, located in coding exon 12 of the PMS2 gene, results from a deletion of two nucleotides at nucleotide positions 2026 to 2027, causing a translational frameshift with a predicted alternate stop codon (p.M676Gfs*7). 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)
|
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:
The c.2026_2027delAT pathogenic mutation, located in coding exon 12 of the PMS2 gene, results from a deletion of two nucleotides at nucleotide positions 2026 to 2027, causing a translational frameshift with a predicted alternate stop codon (p.M676Gfs*7). 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| 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 01, 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.