ClinVar Genomic variation as it relates to human health
NM_000251.3(MSH2):c.138C>G (p.His46Gln)
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.138C>G (p.His46Gln)
Variation ID: 90654 Accession: VCV000090654.45
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 2p21 2: 47403329 (GRCh38) [ NCBI UCSC ] 2: 47630468 (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 Jun 9, 2014 Mar 16, 2024 Dec 19, 2018 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000251.3:c.138C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000242.1:p.His46Gln missense NM_001258281.1:c.-30-31C>G intron variant NC_000002.12:g.47403329C>G NC_000002.11:g.47630468C>G NG_007110.2:g.5206C>G LRG_218:g.5206C>G LRG_218t1:c.138C>G LRG_218p1:p.His46Gln P43246:p.His46Gln - Protein change
- H46Q
- Other names
- p.H46Q:CAC>CAG
- Canonical SPDI
- NC_000002.12:47403328: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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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00019
The Genome Aggregation Database (gnomAD), exomes 0.00022
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00023
Trans-Omics for Precision Medicine (TOPMed) 0.00026
Exome Aggregation Consortium (ExAC) 0.00031
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 | - |
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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Likely benign (1) |
criteria provided, single submitter
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Jan 30, 2024 | RCV000076150.26 | |
Likely benign (3) |
criteria provided, multiple submitters, no conflicts
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Jan 3, 2022 | RCV000115501.20 | |
Conflicting interpretations of pathogenicity (5) |
criteria provided, conflicting classifications
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Aug 15, 2023 | RCV000121555.30 | |
Uncertain significance (1) |
no assertion criteria provided
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Jun 1, 2014 | RCV000148631.10 | |
Likely benign (2) |
reviewed by expert panel
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Dec 19, 2018 | RCV000664309.15 | |
Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
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Feb 27, 2023 | RCV000986643.15 | |
Likely benign (1) |
no assertion criteria provided
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- | RCV001354246.9 | |
Uncertain significance (1) |
criteria provided, single submitter
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Dec 9, 2020 | RCV001798265.10 | |
Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
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Apr 26, 2023 | RCV001719811.12 | |
Likely benign (1) |
criteria provided, single submitter
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Apr 25, 2022 | RCV002477217.8 | |
Likely benign (1) |
criteria provided, single submitter
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Aug 14, 2023 | RCV003935012.1 | |
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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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Likely benign
(Dec 19, 2018)
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reviewed by expert panel
Method: curation
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Lynch syndrome
Affected status: yes
Allele origin:
germline
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International Society for Gastrointestinal Hereditary Tumours (InSiGHT)
Accession: SCV000107166.4
First in ClinVar: Dec 19, 2013 Last updated: Jun 02, 2019 |
Comment:
Multifactorial likelihood analysis posterior probability <0.05
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Uncertain significance
(Mar 28, 2016)
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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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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000539682.1
First in ClinVar: Apr 08, 2017 Last updated: Apr 08, 2017 |
Comment:
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or … (more)
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: ClinVar: 5 labs classify as VUS, including expert panel. No new information suggesting disease-causing role since expert classification. (less)
Method: Genome/Exome Filtration
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Likely benign
(Apr 26, 2018)
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criteria provided, single submitter
Method: research
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Lynch syndrome
(Autosomal dominant inheritance)
Affected status: no
Allele origin:
germline
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University of Washington Department of Laboratory Medicine, University of Washington
Accession: SCV000788241.2
First in ClinVar: Jul 28, 2018 Last updated: Feb 23, 2019 |
Comment:
The MSH2 variant designated as NM_000251.2:c.138C>G (p.His46Gln) is classified as likely benign. This variant is listed in population databases and is found in approximately 1 … (more)
The MSH2 variant designated as NM_000251.2:c.138C>G (p.His46Gln) is classified as likely benign. This variant is listed in population databases and is found in approximately 1 out of 950 individuals of European ancestry, which is not consistent with the prevalence of Lynch syndrome. The variant has been seen in tumors with molecular phenotypes inconsistent with Lynch syndrome (InSiGHT.org). Based on in-silico scores the variant has a prior probability of pathogenicity of 10% or lower (Thompson et al., 2013, PMID:22949379). Cosegregation analysis of two observed families was performed using analyze.myvariant.org (Rañola et al, 2018, PMID:28965303) yielded a combined likelihood ratio of 1.52:1 for this variant explaining cancer in the families (Thompson, et al., 2003, PMID:2900794). However, Bayesian analysis integrating all data (Tavtigian et al, 2018, PMID:29300386) gave a less than 1% probability of pathogenicity, which is consistent with a classification of likely benign. This variant is not predicted to alter MSH2 function or modify cancer risk. A modest (less than 2 fold) increase in cancer risk due to this variant cannot be entirely excluded. This analysis was performed in conjunction with the family studies project as part of the University of Washington Find My Variant Study. (less)
Family history: no
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Uncertain significance
(Apr 27, 2017)
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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: SCV001302263.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. (less)
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Uncertain significance
(Dec 09, 2020)
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criteria provided, single submitter
Method: clinical testing
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Breast and/or ovarian cancer
Affected status: unknown
Allele origin:
germline
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CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
Accession: SCV002042089.1
First in ClinVar: Jan 01, 2022 Last updated: Jan 01, 2022 |
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Likely benign
(Apr 19, 2021)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: no
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV002070914.1
First in ClinVar: Jan 29, 2022 Last updated: Jan 29, 2022 |
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Likely benign
(Jun 26, 2021)
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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: SCV002528846.1
First in ClinVar: Mar 25, 2020 Last updated: Mar 25, 2020 |
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Likely benign
(Dec 13, 2018)
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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: SCV000172719.8
First in ClinVar: Aug 06, 2014 Last updated: Nov 29, 2022 |
Comment:
This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, … (more)
This alteration is classified as likely 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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Likely benign
(Apr 22, 2020)
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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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Genetics and Molecular Pathology, SA Pathology
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002761451.1
First in ClinVar: Dec 17, 2022 Last updated: Dec 17, 2022 |
Comment:
The MSH2 c.138C>G variant is classified as Likely Benign (BS4, BP6, PP3) The MSH2 c.138C>G variant is a single nucleotide change in exon 1 of … (more)
The MSH2 c.138C>G variant is classified as Likely Benign (BS4, BP6, PP3) The MSH2 c.138C>G variant is a single nucleotide change in exon 1 of 16 of the MSH2 gene, which is predicted to change the amino acid histidine at position 46 in the protein to glutamine. This variant does not segregate with disease (BS4). PMID: 28195393- segregation analysis does not support pathogenicity. Variant identified in 0 out of 3 affected family members and 3 out of 9 unaffected family members. PMID:30374176 - family studies do not support pathogenicity (less)
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Likely benign
(Apr 25, 2022)
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criteria provided, single submitter
Method: clinical testing
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Lynch syndrome 1
Muir-Torré syndrome Mismatch repair cancer syndrome 2
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV000895477.2
First in ClinVar: Mar 31, 2019 Last updated: Dec 31, 2022 |
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Likely benign
(Feb 27, 2023)
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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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Mendelics
Accession: SCV001135691.2
First in ClinVar: Jan 13, 2020 Last updated: Mar 04, 2023 |
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Likely benign
(Apr 14, 2021)
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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: SCV000149410.14
First in ClinVar: May 17, 2014 Last updated: Mar 04, 2023 |
Comment:
This variant is associated with the following publications: (PMID: 15872200, 27153395, 18383312, 24728327, 25637381, 23047549, 19389263, 15520370, 16741161, 18033691, 27601186, 28195393, 26333163, 26344056, 29212164, 28330790, … (more)
This variant is associated with the following publications: (PMID: 15872200, 27153395, 18383312, 24728327, 25637381, 23047549, 19389263, 15520370, 16741161, 18033691, 27601186, 28195393, 26333163, 26344056, 29212164, 28330790, 28125075, 28874130, 24055113, 25479140, 26951660, 29368341, 30374176, 31297992) (less)
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Likely benign
(Jul 10, 2023)
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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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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000696213.4
First in ClinVar: Mar 17, 2018 Last updated: Aug 26, 2023 |
Comment:
Variant summary: MSH2 c.138C>G (p.His46Gln) results in a non-conservative amino acid change located in the N-terminal domain (IPR007695) of the encoded protein sequence. Five of … (more)
Variant summary: MSH2 c.138C>G (p.His46Gln) results in a non-conservative amino acid change located in the N-terminal domain (IPR007695) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00026 in 247506 control chromosomes, predominantly at a frequency of 0.00047 within the Non-Finnish European subpopulation in the gnomAD database, including 1 homozygotes. This frequency is not significantly higher than estimated for a pathogenic variant in MSH2 causing Hereditary Nonpolyposis Colorectal Cancer (0.00026 vs 0.00057), allowing no conclusion about variant significance. c.138C>G has been identified in numerous patients with colorectal cancer (CRC), prostate cancer and ovarian cancer without strong evidence for causality (Examples: Barnetson_2008, Hampel_2005, Pal_2012, Grant_2015, Arora_2015, Lagerstedt-Robinson_2016, Maxwell_2016, Ghazani_2017, Raskin_2017, Rossi_2017, Velho_2018, Young_2018, Li_2020, Li_2021). In several studies, microsatellite stability in tumor tissues was assayed and found to be stable and immunohistochemical studies showed the presence of MSH2 (and MSH6) protein (Barnetson_2008, Hampel_2005, Arora_2015). In one patient, MLH1 was found to be hypermethylated at its promoter. This decreases the likelihood of this variant being a cause of germline inherited cancer as MLH1 promoter hypermethylation is associated with sporadic cancers instead of inherited cancers (Hampel_2005). In addition, one study reported the variant to not segregate with disease in a family, i.e. three affected individuals did not carry the variant, while three unaffected individuals carried the variant (Hansen_2017). Two independent in vitro functional studies demonstrated that the variant of interest does not impact mismatch repair activity (Houlleberghs_2016, Jia_2021). Another study that was performed on lymphoblastoid cells from a sporadic CRC patient who carried the variant, found increased level of DNA damage after UV treatment (Arora_2015). Since the patient's tumor sample showed stable microsatellites and normal expression of mismatch repair (MMR) proteins, the authors postulated that beyond its function in MMR, this variant might predispose to DNA double-strand breaks by affecting homologous recombinational repair. The following publications have been ascertained in the context of this evaluation (PMID: 18383312, 18033691, 15872200, 15520370, 23047549, 16574953, 25479140, 26951660, 27601186, 27153395, 28195393, 26344056, 28874130, 29212164, 28125075, 29945567, 29368341, 30374176, 31391288, 33471991, 33357406, 34117267). Multiple submitters including one expert panel (InSiGHT), have cited clinical-significance assessments for this variant to ClinVar after 2014 and classified as likely benign (n=12) and VUS (n=3). Based on the evidence outlined above, the variant was classified as likely benign. (less)
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Uncertain significance
(Apr 26, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV004220947.1
First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 |
Comment:
In the published literature, this variant has been reported in individuals with colorectal cancer and/or multiple adenomatous polyps (PMIDs: 15520370 (2004), 18033691 (2008), 28195393 (2017), … (more)
In the published literature, this variant has been reported in individuals with colorectal cancer and/or multiple adenomatous polyps (PMIDs: 15520370 (2004), 18033691 (2008), 28195393 (2017), 29212164 (2017)), ovarian cancer (PMID: 23047549 (2012)), breast cancer (PMIDs: 27153395 (2016), 29212164 (2017), 33471991 (2021), 35264596 (2022)), pancreatic cancer (PMID: 29945567 (2018)), and gliosarcomas (PMID: 33580181 (2021)). The variant has also been reported in unaffected individuals (PMIDs: 25637381 (2015), 33471991 (2021), 34117267 (2021)). Functional studies have conflicting reports as to whether the variant impacts MSH2 protein expression, stability, and repair (PMIDs: 1587220 (2005), 18033691 (2008), 26344056 (2015), 26344056 (2015), 26951660 (2016), 29212164 (2017), 33357406 (2021)). The frequency of this variant in the general population, 0.00073 (35/47650 chromosomes in North-Western European subpopulation (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is higher than would generally be expected for pathogenic variants in this gene. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is benign or damaging. Based on the available information, we are unable to determine the clinical significance of this variant. (less)
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Likely benign
(Jan 03, 2022)
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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: SCV000537523.3
First in ClinVar: Sep 24, 2016 Last updated: Feb 14, 2024 |
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Likely benign
(Jan 30, 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: SCV000166262.14
First in ClinVar: Jun 15, 2014 Last updated: Feb 20, 2024 |
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Likely benign
(Aug 14, 2023)
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criteria provided, single submitter
Method: clinical testing
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MSH2-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004749235.1
First in ClinVar: Mar 16, 2024 Last updated: Mar 16, 2024 |
Comment:
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
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Likely benign
(Aug 15, 2023)
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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: SCV002552183.4
First in ClinVar: Jul 27, 2022 Last updated: Aug 18, 2023 |
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Uncertain significance
(Jun 01, 2014)
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no assertion criteria provided
Method: research
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Colorectal cancer
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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CSER _CC_NCGL, University of Washington
Study: ESP 6500 variant annotation
Accession: SCV000190346.1 First in ClinVar: Dec 06, 2014 Last updated: Dec 06, 2014 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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Malignant tumor of breast
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: SCV001548810.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021 |
Comment:
The MSH2 p.His46Gln variant was identified in 8 of 8869 proband chromosomes (frequency: 0.0009) from individuals or families with Lynch Syndrome, colorectal cancer, multiple adenomas, … (more)
The MSH2 p.His46Gln variant was identified in 8 of 8869 proband chromosomes (frequency: 0.0009) from individuals or families with Lynch Syndrome, colorectal cancer, multiple adenomas, pancreatic cancer, or ovarian cancer and was identified in 1 of 3326 control chromosomes (frequency: 0.0003) from healthy individuals (Barnetson 2008, Fearnhead 2004, Grant 2015, Hampel 2005, Hansen 2017, Lagerstedt-Robinson 2016, Pal 2012, Rossi 2017). Segregation analysis of the variant in one family with colorectal cancer did not support pathogenicity as the variant was seen in both affected and unaffected family members (Hansen 2017). One study found the variant to be non-pathogenic using a site-specific mutagenesis screen (Houlleberghs 2016). The variant was identified in dbSNP (ID: rs33946261) as “With Likely benign, other allele”, ClinVar (classified as uncertain significance by an InSiGHT expert panel in 2015, Invitae, Color, and four other submitters; and as likely benign by GeneDx, Ambry Genetics, and one other submitter), UMD-LSDB (classified as UV), and Mismatch Repair Genes Variant Database. The variant was identified in control databases in 58 of 256068 chromosomes (1 homozygous) at a frequency of 0.0002 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: European in 55 (1 homozygous) of 115892 chromosomes (freq: 0.0005), African in 1 of 21856 chromosomes (freq: 0.00005), and Latino in 2 of 32620 chromosomes (freq: 0.00006); it was not observed in the “Other”, Ashkenazi Jewish, East Asian, European Finnish, or South Asian populations. The p.His46 residue is conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and 2 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. (less)
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not provided
(Sep 19, 2013)
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no classification provided
Method: reference population
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AllHighlyPenetrant
Affected status: unknown
Allele origin:
germline
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ITMI
Accession: SCV000085749.1
First in ClinVar: Jun 09, 2014 Last updated: Jun 09, 2014 |
Observation 1:
Ethnicity/Population group: Whole_cohort
Observation 2:
Ethnicity/Population group: African
Observation 3:
Ethnicity/Population group: African_European
Observation 4:
Ethnicity/Population group: Central_Asian
Observation 5:
Ethnicity/Population group: East_Asian
Observation 6:
Ethnicity/Population group: European
Observation 7:
Ethnicity/Population group: Hispanic
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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 germline variants in Brazilian breast cancer patients using multigene panel testing. | Guindalini RSC | Scientific reports | 2022 | PMID: 35264596 |
Investigation of monogenic causes of familial breast cancer: data from the BEACCON case-control study. | Li N | NPJ breast cancer | 2021 | PMID: 34117267 |
Hypermutated phenotype in gliosarcoma of the spinal cord. | Hong CS | NPJ precision oncology | 2021 | PMID: 33580181 |
Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women. | Breast Cancer Association Consortium | The New England journal of medicine | 2021 | PMID: 33471991 |
Massively parallel functional testing of MSH2 missense variants conferring Lynch syndrome risk. | Jia X | American journal of human genetics | 2021 | PMID: 33357406 |
Tumour characteristics provide evidence for germline mismatch repair missense variant pathogenicity. | Li S | Journal of medical genetics | 2020 | PMID: 31391288 |
Comprehensive mismatch repair gene panel identifies variants in patients with Lynch-like syndrome. | Xavier A | Molecular genetics & genomic medicine | 2019 | PMID: 31297992 |
Outcomes of 92 patient-driven family studies for reclassification of variants of uncertain significance. | Tsai GJ | Genetics in medicine : official journal of the American College of Medical Genetics | 2019 | PMID: 30374176 |
Pancreatic cancer as a sentinel for hereditary cancer predisposition. | Young EL | BMC cancer | 2018 | PMID: 29945567 |
Intraductal/ductal histology and lymphovascular invasion are associated with germline DNA-repair gene mutations in prostate cancer. | Isaacsson Velho P | The Prostate | 2018 | PMID: 29368341 |
Targeted sequencing of established and candidate colorectal cancer genes in the Colon Cancer Family Registry Cohort. | Raskin L | Oncotarget | 2017 | PMID: 29212164 |
A survey of the clinicopathological and molecular characteristics of patients with suspected Lynch syndrome in Latin America. | Rossi BM | BMC cancer | 2017 | PMID: 28874130 |
Use of multigene-panel identifies pathogenic variants in several CRC-predisposing genes in patients previously tested for Lynch Syndrome. | Hansen MF | Clinical genetics | 2017 | PMID: 28195393 |
Assigning clinical meaning to somatic and germ-line whole-exome sequencing data in a prospective cancer precision medicine study. | Ghazani AA | Genetics in medicine : official journal of the American College of Medical Genetics | 2017 | PMID: 28125075 |
Mismatch repair gene mutation spectrum in the Swedish Lynch syndrome population. | Lagerstedt-Robinson K | Oncology reports | 2016 | PMID: 27601186 |
Evaluation of ACMG-Guideline-Based Variant Classification of Cancer Susceptibility and Non-Cancer-Associated Genes in Families Affected by Breast Cancer. | Maxwell KN | American journal of human genetics | 2016 | PMID: 27153395 |
Oligonucleotide-directed mutagenesis screen to identify pathogenic Lynch syndrome-associated MSH2 DNA mismatch repair gene variants. | Houlleberghs H | Proceedings of the National Academy of Sciences of the United States of America | 2016 | PMID: 26951660 |
Genetic Variants That Predispose to DNA Double-Strand Breaks in Lymphocytes From a Subset of Patients With Familial Colorectal Carcinomas. | Arora S | Gastroenterology | 2015 | PMID: 26344056 |
Classification of Amino Acid Substitutions in Mismatch Repair Proteins Using PON-MMR2. | Niroula A | Human mutation | 2015 | PMID: 26333163 |
Actionable exomic incidental findings in 6503 participants: challenges of variant classification. | Amendola LM | Genome research | 2015 | PMID: 25637381 |
Prevalence of germline mutations in cancer predisposition genes in patients with pancreatic cancer. | Grant RC | Gastroenterology | 2015 | PMID: 25479140 |
Germline variation in cancer-susceptibility genes in a healthy, ancestrally diverse cohort: implications for individual genome sequencing. | Bodian DL | PloS one | 2014 | PMID: 24728327 |
Frequency of mutations in mismatch repair genes in a population-based study of women with ovarian cancer. | Pal T | British journal of cancer | 2012 | PMID: 23047549 |
Investigation on the role of nsSNPs in HNPCC genes--a bioinformatics approach. | Doss CG | Journal of biomedical science | 2009 | PMID: 19389263 |
Accurate classification of MLH1/MSH2 missense variants with multivariate analysis of protein polymorphisms-mismatch repair (MAPP-MMR). | Chao EC | Human mutation | 2008 | PMID: 18383312 |
Classification of ambiguous mutations in DNA mismatch repair genes identified in a population-based study of colorectal cancer. | Barnetson RA | Human mutation | 2008 | PMID: 18033691 |
Variants in the ATM-BRCA2-CHEK2 axis predispose to chronic lymphocytic leukemia. | Rudd MF | Blood | 2006 | PMID: 16574953 |
Screening for the Lynch syndrome (hereditary nonpolyposis colorectal cancer). | Hampel H | The New England journal of medicine | 2005 | PMID: 15872200 |
Multiple rare variants in different genes account for multifactorial inherited susceptibility to colorectal adenomas. | Fearnhead NS | Proceedings of the National Academy of Sciences of the United States of America | 2004 | PMID: 15520370 |
Molecular basis of HNPCC: mutations of MMR genes. | Papadopoulos N | Human mutation | 1997 | PMID: 9259192 |
Microsatellite instability and the role of hMSH2 in sporadic colorectalcancer. | Bubb VJ | Oncogene | 1996 | PMID: 8700523 |
http://www.insight-database.org/classifications/?gene=MSH2&variant=c.138C%3EG | - | - | - | - |
http://www.insight-database.org/classifications/index.html?gene=MSH2&variant=c.138C%3EG | - | - | - | - |
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Text-mined citations for rs33946261 ...
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.