The p.K690* pathogenic mutation (also known as c.2068A>T), located in coding exon 12 of the PMS2 gene, results from an A to T substitution at nucleotide position 2068. This changes the amino acid from a lysine to a stop codon within coding exon 12. 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.2068A>T (p.Lys690Ter)
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.2068A>T (p.Lys690Ter)
Variation ID: 1785318 Accession: VCV001785318.2
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 7p22.1 7: 5982930 (GRCh38) [ NCBI UCSC ] 7: 6022561 (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 2, 2019 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000535.7:c.2068A>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000526.2:p.Lys690Ter nonsense NM_001018040.1:c.1663A>T NP_001018050.1:p.Lys555Ter nonsense NM_001322003.2:c.1663A>T NP_001308932.1:p.Lys555Ter nonsense NM_001322004.2:c.1663A>T NP_001308933.1:p.Lys555Ter nonsense NM_001322005.2:c.1663A>T NP_001308934.1:p.Lys555Ter nonsense NM_001322006.2:c.1912A>T NP_001308935.1:p.Lys638Ter nonsense NM_001322007.2:c.1750A>T NP_001308936.1:p.Lys584Ter nonsense NM_001322008.2:c.1750A>T NP_001308937.1:p.Lys584Ter nonsense NM_001322009.2:c.1663A>T NP_001308938.1:p.Lys555Ter nonsense NM_001322010.2:c.1507A>T NP_001308939.1:p.Lys503Ter nonsense NM_001322011.2:c.1135A>T NP_001308940.1:p.Lys379Ter nonsense NM_001322012.2:c.1135A>T NP_001308941.1:p.Lys379Ter nonsense NM_001322013.2:c.1495A>T NP_001308942.1:p.Lys499Ter nonsense NM_001322014.2:c.2068A>T NP_001308943.1:p.Lys690Ter nonsense NM_001322015.2:c.1759A>T NP_001308944.1:p.Lys587Ter nonsense NM_001406866.1:c.2254A>T NP_001393795.1:p.Lys752Ter nonsense NM_001406868.1:c.2092A>T NP_001393797.1:p.Lys698Ter nonsense NM_001406869.1:c.1960A>T NP_001393798.1:p.Lys654Ter nonsense NM_001406870.1:c.1912A>T NP_001393799.1:p.Lys638Ter nonsense NM_001406871.1:c.2068A>T NP_001393800.1:p.Lys690Ter nonsense NM_001406873.1:c.1870A>T NP_001393802.1:p.Lys624Ter nonsense NM_001406874.1:c.1900A>T NP_001393803.1:p.Lys634Ter nonsense NM_001406875.1:c.1759A>T NP_001393804.1:p.Lys587Ter nonsense NM_001406876.1:c.1750A>T NP_001393805.1:p.Lys584Ter nonsense NM_001406877.1:c.1759A>T NP_001393806.1:p.Lys587Ter nonsense NM_001406878.1:c.1759A>T NP_001393807.1:p.Lys587Ter nonsense NM_001406879.1:c.1759A>T NP_001393808.1:p.Lys587Ter nonsense NM_001406880.1:c.1759A>T NP_001393809.1:p.Lys587Ter nonsense NM_001406881.1:c.1759A>T NP_001393810.1:p.Lys587Ter nonsense NM_001406882.1:c.1759A>T NP_001393811.1:p.Lys587Ter nonsense NM_001406883.1:c.1750A>T NP_001393812.1:p.Lys584Ter nonsense NM_001406884.1:c.1744A>T NP_001393813.1:p.Lys582Ter nonsense NM_001406885.1:c.1732A>T NP_001393814.1:p.Lys578Ter nonsense NM_001406886.1:c.1702A>T NP_001393815.1:p.Lys568Ter nonsense NM_001406887.1:c.1663A>T NP_001393816.1:p.Lys555Ter nonsense NM_001406888.1:c.1663A>T NP_001393817.1:p.Lys555Ter nonsense NM_001406889.1:c.1663A>T NP_001393818.1:p.Lys555Ter nonsense NM_001406890.1:c.1663A>T NP_001393819.1:p.Lys555Ter nonsense NM_001406891.1:c.1663A>T NP_001393820.1:p.Lys555Ter nonsense NM_001406892.1:c.1663A>T NP_001393821.1:p.Lys555Ter nonsense NM_001406893.1:c.1663A>T NP_001393822.1:p.Lys555Ter nonsense NM_001406894.1:c.1663A>T NP_001393823.1:p.Lys555Ter nonsense NM_001406895.1:c.1663A>T NP_001393824.1:p.Lys555Ter nonsense NM_001406896.1:c.1663A>T NP_001393825.1:p.Lys555Ter nonsense NM_001406897.1:c.1663A>T NP_001393826.1:p.Lys555Ter nonsense NM_001406898.1:c.1663A>T NP_001393827.1:p.Lys555Ter nonsense NM_001406899.1:c.1663A>T NP_001393828.1:p.Lys555Ter nonsense NM_001406900.1:c.1603A>T NP_001393829.1:p.Lys535Ter nonsense NM_001406901.1:c.1594A>T NP_001393830.1:p.Lys532Ter nonsense NM_001406902.1:c.1594A>T NP_001393831.1:p.Lys532Ter nonsense NM_001406904.1:c.1555A>T NP_001393833.1:p.Lys519Ter nonsense NM_001406905.1:c.1555A>T NP_001393834.1:p.Lys519Ter nonsense NM_001406906.1:c.1507A>T NP_001393835.1:p.Lys503Ter nonsense NM_001406907.1:c.1507A>T NP_001393836.1:p.Lys503Ter nonsense NM_001406909.1:c.1495A>T NP_001393838.1:p.Lys499Ter nonsense NM_001406911.1:c.1297A>T NP_001393840.1:p.Lys433Ter nonsense NM_001406912.1:c.865A>T NP_001393841.1:p.Lys289Ter nonsense NR_003085.2:n.2150A>T NR_136154.1:n.2155A>T non-coding transcript variant NC_000007.14:g.5982930T>A NC_000007.13:g.6022561T>A NG_008466.1:g.31177A>T LRG_161:g.31177A>T LRG_161t1:c.2068A>T LRG_161p1:p.Lys690Ter - Protein change
- K289*, K433*, K582*, K654*, K690*, K503*, K519*, K584*, K587*, K624*, K638*, K698*, K752*, K379*, K499*, K532*, K535*, K555*, K568*, K578*, K634*
- Other names
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- Canonical SPDI
- NC_000007.14:5982929:T: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 |
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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Jan 2, 2019 | RCV002422067.2 |
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
(Jan 02, 2019)
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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: SCV002725181.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The p.K690* pathogenic mutation (also known as c.2068A>T), located in coding exon 12 of the PMS2 gene, results from an A to T substitution at … (more)
The p.K690* pathogenic mutation (also known as c.2068A>T), located in coding exon 12 of the PMS2 gene, results from an A to T substitution at nucleotide position 2068. This changes the amino acid from a lysine to a stop codon within coding exon 12. 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 p.K690* pathogenic mutation (also known as c.2068A>T), located in coding exon 12 of the PMS2 gene, results from an A to T substitution at nucleotide position 2068. This changes the amino acid from a lysine to a stop codon within coding exon 12. 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.