ClinVar Genomic variation as it relates to human health
NM_000251.3(MSH2):c.211+9C>G
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.211+9C>G
Variation ID: 36573 Accession: VCV000036573.43
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 2p21 2: 47403411 (GRCh38) [ NCBI UCSC ] 2: 47630550 (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 Apr 4, 2013 Feb 20, 2024 Sep 5, 2013 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000251.3:c.211+9C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
intron variant NM_001258281.1:c.13+9C>G intron variant NC_000002.12:g.47403411C>G NC_000002.11:g.47630550C>G NG_007110.2:g.5288C>G LRG_218:g.5288C>G LRG_218t1:c.211+9C>G - Protein change
- Other names
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- Canonical SPDI
- NC_000002.12:47403410:C:G
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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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0.37161 (C)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.47588
Trans-Omics for Precision Medicine (TOPMed) 0.53119
The Genome Aggregation Database (gnomAD) 0.55454
1000 Genomes Project 0.62839
1000 Genomes Project 30x 0.63086
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
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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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MSH2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
7207 | 7355 |
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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Benign (2) |
reviewed by expert panel
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Sep 5, 2013 | RCV000030249.15 | |
Benign (7) |
criteria provided, multiple submitters, no conflicts
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May 27, 2015 | RCV000035360.37 | |
Benign (5) |
criteria provided, multiple submitters, no conflicts
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Jul 7, 2023 | RCV000144620.16 | |
Benign (3) |
criteria provided, multiple submitters, no conflicts
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Oct 19, 2020 | RCV000448740.11 | |
Benign (1) |
criteria provided, single submitter
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Feb 1, 2024 | RCV000535550.17 | |
Benign (1) |
no assertion criteria provided
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- | RCV001353423.9 | |
Benign (2) |
criteria provided, multiple submitters, no conflicts
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Nov 30, 2023 | RCV001642243.20 |
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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no known pathogenicity
(Sep 05, 2013)
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reviewed by expert panel
Method: research
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Lynch Syndrome
Affected status: unknown
Allele origin:
germline
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International Society for Gastrointestinal Hereditary Tumours (InSiGHT)
Accession: SCV000107420.3
First in ClinVar: Dec 19, 2013 Last updated: Dec 24, 2022 |
Comments (2):
MAF >1%
Converted during submission to Benign.
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Benign
(-)
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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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PreventionGenetics, part of Exact Sciences
Accession: SCV000303162.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
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Benign
(Sep 21, 2015)
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criteria provided, single submitter
Method: clinical testing
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Lynch syndrome 1
Affected status: yes
Allele origin:
germline
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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Study: VKGL Data-share Consensus
Accession: SCV000744264.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
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Benign
(May 27, 2015)
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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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Eurofins Ntd Llc (ga)
Accession: SCV000110275.8
First in ClinVar: Jan 17, 2014 Last updated: May 03, 2018 |
Number of individuals with the variant: 32
Sex: mixed
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Benign
(Dec 03, 2012)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: not provided
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000059008.5
First in ClinVar: May 03, 2013 Last updated: Aug 27, 2017 |
Comment:
211+9C>G in intron 1 of MSH2: This variant is not expected to have clinical sign ificance because it is not located within the conserved +/- … (more)
211+9C>G in intron 1 of MSH2: This variant is not expected to have clinical sign ificance because it is not located within the conserved +/- 1, 2 invariant regio n. It has been identified in 36% (3011/8418) of European American chromosomes fr om a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washi ngton.edu/EVS/; rs23033426). 211+9C>G in intron 1 of MSH2 (rs23033426; allele f requency= 36%, 3011/8418) ** (less)
Number of individuals with the variant: 8
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Benign
(Jan 13, 2018)
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criteria provided, single submitter
Method: clinical testing
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Lynch syndrome 1
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000430910.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
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Benign
(Mar 03, 2015)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV001860169.1
First in ClinVar: Sep 19, 2021 Last updated: Sep 19, 2021 |
Comment:
This variant is associated with the following publications: (PMID: 30093976)
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benign
(Aug 18, 2011)
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criteria provided, single submitter
Method: curation, clinical testing
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Hereditary non-polyposis colon cancer
(autosomal unknown)
Affected status: unknown, yes
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000052916.2
First in ClinVar: Apr 04, 2013 Last updated: Mar 28, 2022 |
Comment:
Converted during submission to Benign.
Observation 1:
Tissue: Blood
Observation 2:
Tissue: Blood
Observation 3:
Tissue: Blood
Observation 4:
Tissue: Blood
Observation 5:
Tissue: Blood
Observation 6:
Tissue: Blood
Observation 7:
Tissue: Blood
Observation 8:
Tissue: Blood
Observation 9:
Tissue: Blood
Observation 10:
Tissue: Blood
Observation 11:
Tissue: Blood
Observation 12:
Tissue: Blood
Observation 13:
Tissue: Blood
Observation 14:
Tissue: Blood
Observation 15:
Tissue: Blood
Observation 16:
Tissue: Blood
Observation 17:
Tissue: Blood
Observation 18:
Tissue: Blood
Observation 19:
Tissue: Blood
Observation 20:
Tissue: Blood
Observation 21:
Tissue: Blood
Observation 22:
Tissue: Blood
Observation 23:
Tissue: Blood
Observation 24:
Tissue: Blood
Observation 25:
Tissue: Blood
Observation 26:
Tissue: Blood
Observation 27:
Tissue: Blood
Observation 28:
Tissue: Blood
Observation 29:
Tissue: Blood
Observation 30:
Tissue: Blood
Observation 31:
Tissue: Blood
Observation 32:
Tissue: Blood
Observation 33:
Tissue: Blood
Observation 34:
Tissue: Blood
Observation 35:
Tissue: Blood
Observation 36:
Tissue: Blood
Observation 37:
Tissue: Blood
Observation 38:
Tissue: Blood
Observation 39:
Tissue: Blood
Observation 40:
Tissue: Blood
Observation 41:
Tissue: Blood
Observation 42:
Tissue: Blood
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Benign
(Jul 07, 2023)
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criteria provided, single submitter
Method: clinical testing
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Lynch syndrome 1
Affected status: yes
Allele origin:
germline
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KCCC/NGS Laboratory, Kuwait Cancer Control Center
Accession: SCV004015930.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023 |
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Benign
(Nov 30, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000604250.9
First in ClinVar: Aug 27, 2017 Last updated: Feb 20, 2024 |
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Benign
(Dec 01, 2014)
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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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Color Diagnostics, LLC DBA Color Health
Accession: SCV000537324.1
First in ClinVar: Mar 25, 2017 Last updated: Mar 25, 2017 |
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Benign
(Oct 19, 2020)
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criteria provided, single submitter
Method: curation
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Sema4, Sema4
Accession: SCV002534446.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022 |
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Benign
(Nov 18, 2014)
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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: SCV002726369.1
First in ClinVar: Nov 29, 2022 Last updated: Nov 29, 2022 |
Comment:
This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA … (more)
This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
Number of individuals with the variant: 1
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Benign
(Feb 01, 2024)
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criteria provided, single submitter
Method: clinical testing
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Hereditary nonpolyposis colorectal neoplasms
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000625350.7
First in ClinVar: Dec 26, 2017 Last updated: Feb 14, 2024 |
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Benign
(Jul 24, 2014)
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no assertion criteria provided
Method: clinical testing
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Lynch syndrome I
Affected status: unknown
Allele origin:
germline
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Pathway Genomics
Accession: SCV000189947.1
First in ClinVar: Oct 19, 2014 Last updated: Oct 19, 2014 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
unknown
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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV000257168.2
First in ClinVar: Nov 20, 2015 Last updated: Aug 27, 2017 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001906300.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Clinical Genetics, Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001925124.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001953620.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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Lynch syndrome 1
Affected status: yes
Allele origin:
germline
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Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV000734196.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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Carcinoma of colon
Affected status: yes
Allele origin:
unknown
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Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000592456.2 First in ClinVar: Aug 27, 2017 Last updated: Apr 13, 2021 |
Comment:
The c.211+9C>G variant is not expected to have clinical significance because it is not located in the conserved region of the splicing consensus sequence. Furthermore, … (more)
The c.211+9C>G variant is not expected to have clinical significance because it is not located in the conserved region of the splicing consensus sequence. Furthermore, this variant is reported as a common polymorphism in dbSNP (rs2303426) and reported as a benign polymorphism in the literature. Average Heterozygosity: 0.488+/-0.075 (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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DNA repair polymorphisms and the risk of stomach adenocarcinoma and severe chronic gastritis in the EPIC-EURGAST study. | Capellá G | International journal of epidemiology | 2008 | PMID: 18641418 |
Systematic analysis of hMSH2 and hMLH1 in young colon cancer patients and controls. | Farrington SM | American journal of human genetics | 1998 | PMID: 9718327 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=MSH2 | - | - | - | - |
http://www.insight-database.org/classifications/index.html?gene=MSH2&variant=c.211%2B9C%3EG | - | - | - | - |
Text-mined citations for rs2303426 ...
HelpRecord last updated Apr 15, 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.