ClinVar Genomic variation as it relates to human health
NM_000251.3(MSH2):c.2021G>T (p.Gly674Val)
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000251.3(MSH2):c.2021G>T (p.Gly674Val)
Variation ID: 1784570 Accession: VCV001784570.2
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 2p21 2: 47476382 (GRCh38) [ NCBI UCSC ] 2: 47703521 (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 24, 2021 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000251.3:c.2021G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000242.1:p.Gly674Val missense NM_001258281.1:c.1823G>T NP_001245210.1:p.Gly608Val missense NM_001406631.1:c.2021G>T NP_001393560.1:p.Gly674Val missense NM_001406632.1:c.2021G>T NP_001393561.1:p.Gly674Val missense NM_001406633.1:c.2021G>T NP_001393562.1:p.Gly674Val missense NM_001406634.1:c.2021G>T NP_001393563.1:p.Gly674Val missense NM_001406635.1:c.2021G>T NP_001393564.1:p.Gly674Val missense NM_001406636.1:c.1988G>T NP_001393565.1:p.Gly663Val missense NM_001406637.1:c.2021G>T NP_001393566.1:p.Gly674Val missense NM_001406638.1:c.2060G>T NP_001393567.1:p.Gly687Val missense NM_001406639.1:c.2021G>T NP_001393568.1:p.Gly674Val missense NM_001406640.1:c.2021G>T NP_001393569.1:p.Gly674Val missense NM_001406641.1:c.2021G>T NP_001393570.1:p.Gly674Val missense NM_001406642.1:c.2021G>T NP_001393571.1:p.Gly674Val missense NM_001406643.1:c.2021G>T NP_001393572.1:p.Gly674Val missense NM_001406644.1:c.2021G>T NP_001393573.1:p.Gly674Val missense NM_001406645.1:c.2021G>T NP_001393574.1:p.Gly674Val missense NM_001406646.1:c.2021G>T NP_001393575.1:p.Gly674Val missense NM_001406647.1:c.1871G>T NP_001393576.1:p.Gly624Val missense NM_001406648.1:c.2021G>T NP_001393577.1:p.Gly674Val missense NM_001406649.1:c.1871G>T NP_001393578.1:p.Gly624Val missense NM_001406650.1:c.1871G>T NP_001393579.1:p.Gly624Val missense NM_001406651.1:c.1871G>T NP_001393580.1:p.Gly624Val missense NM_001406652.1:c.1871G>T NP_001393581.1:p.Gly624Val missense NM_001406653.1:c.1961G>T NP_001393582.1:p.Gly654Val missense NM_001406654.1:c.1601G>T NP_001393583.1:p.Gly534Val missense NM_001406656.1:c.1124G>T NP_001393585.1:p.Gly375Val missense NM_001406658.1:c.665G>T NP_001393587.1:p.Gly222Val missense NM_001406659.1:c.665G>T NP_001393588.1:p.Gly222Val missense NM_001406660.1:c.665G>T NP_001393589.1:p.Gly222Val missense NM_001406661.1:c.665G>T NP_001393590.1:p.Gly222Val missense NM_001406662.1:c.665G>T NP_001393591.1:p.Gly222Val missense NM_001406669.1:c.665G>T NP_001393598.1:p.Gly222Val missense NM_001406674.1:c.2021G>T NP_001393603.1:p.Gly674Val missense NR_176230.1:n.2057G>T NR_176231.1:n.2057G>T NR_176232.1:n.2057G>T NR_176233.1:n.1899G>T NR_176234.1:n.2057G>T NR_176235.1:n.2057G>T NR_176236.1:n.2057G>T NR_176237.1:n.2057G>T NR_176238.1:n.2190G>T NR_176239.1:n.2057G>T NR_176241.1:n.2057G>T NR_176242.1:n.2057G>T NR_176243.1:n.1907G>T NR_176244.1:n.2057G>T NR_176245.1:n.2057G>T NR_176246.1:n.2057G>T NR_176247.1:n.2057G>T NR_176248.1:n.2057G>T NR_176249.1:n.2287G>T NR_176250.1:n.1797G>T NC_000002.12:g.47476382G>T NC_000002.11:g.47703521G>T NG_007110.2:g.78259G>T LRG_218:g.78259G>T LRG_218t1:c.2021G>T LRG_218p1:p.Gly674Val - Protein change
- G608V, G674V, G534V, G624V, G654V, G222V, G663V, G687V, G375V
- Other names
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- Canonical SPDI
- NC_000002.12:47476381:G:T
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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 |
7401 | 7563 |
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
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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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Mar 24, 2021 | RCV002419599.2 |
Submissions - Germline
Classification
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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
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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
(Mar 24, 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: SCV002724384.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The p.G674V variant (also known as c.2021G>T), located in coding exon 13 of the MSH2 gene, results from a G to T substitution at nucleotide … (more)
The p.G674V variant (also known as c.2021G>T), located in coding exon 13 of the MSH2 gene, results from a G to T substitution at nucleotide position 2021. The glycine at codon 674 is replaced by valine, an amino acid with dissimilar properties. Alterations at the same codon, p.G674D and p.G674S, have demonstrated reduced function in several studies (Drotschmann K et al. Proc. Natl. Acad. Sci. U.S.A., 1999 Mar;96:2970-5; Studamire B et al. Mol. Cell. Biol., 1999 Nov;19:7558-67; Bowers J et al. J. Mol. Biol., 2000 Sep;302:327-38; Heinen CD et al. Cancer Cell, 2002 Jun;1:469-78; Kijas AW et al. J. Mol. Biol., 2003 Aug;331:123-38; Gammie AE et al. Genetics, 2007 Oct;177:707-21) and p.G674D has been reported in a proband who met clinical criteria for Lynch syndrome (Raedle J et al. Ann. Intern. Med., 2001 Oct;135:566-76; Brieger A et al. Fam. Cancer, 2011 Sep;10:591-5). Based on an internal structural assessment, this alteration disrupts the well-established ATP-binding motif (Warren JJ et al. Mol. Cell, 2007 May;26:579-92). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly 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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Structure of the human MutSalpha DNA lesion recognition complex. | Warren JJ | Molecular cell | 2007 | PMID: 17531815 |
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.