ClinVar Genomic variation as it relates to human health
NM_000251.3(MSH2):c.1829A>C (p.His610Pro)
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.
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.
Likely pathogenic(2); Uncertain significance(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000251.3(MSH2):c.1829A>C (p.His610Pro)
Variation ID: 1780893 Accession: VCV001780893.4
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 2p21 2: 47475094 (GRCh38) [ NCBI UCSC ] 2: 47702233 (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 Feb 6, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000251.3:c.1829A>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000242.1:p.His610Pro missense NM_001258281.1:c.1631A>C NP_001245210.1:p.His544Pro missense NM_001406631.1:c.1829A>C NP_001393560.1:p.His610Pro missense NM_001406632.1:c.1829A>C NP_001393561.1:p.His610Pro missense NM_001406633.1:c.1829A>C NP_001393562.1:p.His610Pro missense NM_001406634.1:c.1829A>C NP_001393563.1:p.His610Pro missense NM_001406635.1:c.1829A>C NP_001393564.1:p.His610Pro missense NM_001406636.1:c.1796A>C NP_001393565.1:p.His599Pro missense NM_001406637.1:c.1829A>C NP_001393566.1:p.His610Pro missense NM_001406638.1:c.1868A>C NP_001393567.1:p.His623Pro missense NM_001406639.1:c.1829A>C NP_001393568.1:p.His610Pro missense NM_001406640.1:c.1829A>C NP_001393569.1:p.His610Pro missense NM_001406641.1:c.1829A>C NP_001393570.1:p.His610Pro missense NM_001406642.1:c.1829A>C NP_001393571.1:p.His610Pro missense NM_001406643.1:c.1829A>C NP_001393572.1:p.His610Pro missense NM_001406644.1:c.1829A>C NP_001393573.1:p.His610Pro missense NM_001406645.1:c.1829A>C NP_001393574.1:p.His610Pro missense NM_001406646.1:c.1829A>C NP_001393575.1:p.His610Pro missense NM_001406647.1:c.1679A>C NP_001393576.1:p.His560Pro missense NM_001406648.1:c.1829A>C NP_001393577.1:p.His610Pro missense NM_001406649.1:c.1679A>C NP_001393578.1:p.His560Pro missense NM_001406650.1:c.1679A>C NP_001393579.1:p.His560Pro missense NM_001406651.1:c.1679A>C NP_001393580.1:p.His560Pro missense NM_001406652.1:c.1679A>C NP_001393581.1:p.His560Pro missense NM_001406653.1:c.1769A>C NP_001393582.1:p.His590Pro missense NM_001406654.1:c.1409A>C NP_001393583.1:p.His470Pro missense NM_001406655.1:c.1829A>C NP_001393584.1:p.His610Pro missense NM_001406656.1:c.932A>C NP_001393585.1:p.His311Pro missense NM_001406657.1:c.*39A>C NM_001406658.1:c.473A>C NP_001393587.1:p.His158Pro missense NM_001406659.1:c.473A>C NP_001393588.1:p.His158Pro missense NM_001406660.1:c.473A>C NP_001393589.1:p.His158Pro missense NM_001406661.1:c.473A>C NP_001393590.1:p.His158Pro missense NM_001406662.1:c.473A>C NP_001393591.1:p.His158Pro missense NM_001406669.1:c.473A>C NP_001393598.1:p.His158Pro missense NM_001406674.1:c.1829A>C NP_001393603.1:p.His610Pro missense NR_176230.1:n.1865A>C NR_176231.1:n.1865A>C NR_176232.1:n.1865A>C NR_176233.1:n.1707A>C NR_176234.1:n.1865A>C NR_176235.1:n.1865A>C NR_176236.1:n.1865A>C NR_176237.1:n.1865A>C NR_176238.1:n.1998A>C NR_176239.1:n.1865A>C NR_176240.1:n.1865A>C NR_176241.1:n.1865A>C NR_176242.1:n.1865A>C NR_176243.1:n.1715A>C NR_176244.1:n.1865A>C NR_176245.1:n.1865A>C NR_176246.1:n.1865A>C NR_176247.1:n.1865A>C NR_176248.1:n.1865A>C NR_176249.1:n.2095A>C NR_176250.1:n.1605A>C NC_000002.12:g.47475094A>C NC_000002.11:g.47702233A>C NG_007110.2:g.76971A>C LRG_218:g.76971A>C LRG_218t1:c.1829A>C LRG_218p1:p.His610Pro - Protein change
- H470P, H560P, H599P, H623P, H311P, H610P, H544P, H158P, H590P
- Other names
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- Canonical SPDI
- NC_000002.12:47475093:A:C
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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
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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
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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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MSH2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
7325 | 7478 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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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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Likely pathogenic (1) |
criteria provided, single submitter
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Feb 3, 2021 | RCV002410486.2 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Dec 15, 2023 | RCV003482411.1 | |
Uncertain significance (1) |
criteria provided, single submitter
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Feb 6, 2024 | RCV003493949.1 |
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
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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
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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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Likely pathogenic
(Dec 15, 2023)
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criteria provided, single submitter
Method: clinical testing
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Lynch syndrome
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet
Accession: SCV004228504.1
First in ClinVar: Jan 26, 2024 Last updated: Jan 26, 2024 |
Comment:
The following ACMG criteria is used: PM2_Supporting (not reported in gnomAD), PS3 (PMID: 33357406); PP4_Strong (lack of MSH2 ekspression/MSI in three tumors (one CRC and … (more)
The following ACMG criteria is used: PM2_Supporting (not reported in gnomAD), PS3 (PMID: 33357406); PP4_Strong (lack of MSH2 ekspression/MSI in three tumors (one CRC and two endometrial) from three different families (less)
Sex: mixed
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Uncertain significance
(Feb 06, 2024)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV004243565.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
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Likely pathogenic
(Feb 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: SCV002711135.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The p.H610P variant (also known as c.1829A>C), located in coding exon 12 of the MSH2 gene, results from an A to C substitution at nucleotide … (more)
The p.H610P variant (also known as c.1829A>C), located in coding exon 12 of the MSH2 gene, results from an A to C substitution at nucleotide position 1829. The histidine at codon 610 is replaced by proline, an amino acid with similar properties. This alteration has been identified in the germline of individuals whose Lynch syndrome associated tumors demonstrated high microsatellite instability (MSI-H) with absent MSH2/MSH6 expression on immunohistochemistry (IHC) and a somatic pathogenic MSH2 mutation was also identified in one of the cases (Ambry internal data; Okkels H et al. Genet Test Mol Biomarkers. 2019 Sep;23:688-695; Fokkema IF et al. Hum. Mutat. 2011 May;32:557-63). Based on internal structural analysis, this variant is anticipated to result in a significant decrease in structural stability (Gupta S et al. Nat. Struct. Mol. Biol. 2011 Dec;19:72-8). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic. (less)
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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. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Detection of PMS2 Mutations by Screening Hereditary Nonpolyposis Colon Cancer Families from Denmark and Sweden. | Okkels H | Genetic testing and molecular biomarkers | 2019 | PMID: 31433215 |
Mechanism of mismatch recognition revealed by human MutSβ bound to unpaired DNA loops. | Gupta S | Nature structural & molecular biology | 2011 | PMID: 22179786 |
LOVD v.2.0: the next generation in gene variant databases. | Fokkema IF | Human mutation | 2011 | PMID: 21520333 |
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.