ClinVar Genomic variation as it relates to human health
NM_000251.3(MSH2):c.4G>A (p.Ala2Thr)
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
-
NM_000251.3(MSH2):c.4G>A (p.Ala2Thr)
Variation ID: 41650 Accession: VCV000041650.50
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 2p21 2: 47403195 (GRCh38) [ NCBI UCSC ] 2: 47630334 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 12, 2013 Mar 16, 2024 Jun 13, 2018 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_000251.3:c.4G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000242.1:p.Ala2Thr missense NM_001258281.1:c.-31+20G>A intron variant NC_000002.12:g.47403195G>A NC_000002.11:g.47630334G>A NG_007110.2:g.5072G>A LRG_218:g.5072G>A LRG_218t1:c.4G>A LRG_218p1:p.Ala2Thr P43246:p.Ala2Thr - Protein change
- A2T
- Other names
- -
- Canonical SPDI
- NC_000002.12:47403194:G:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
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.
-
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00008
Trans-Omics for Precision Medicine (TOPMed) 0.00010
The Genome Aggregation Database (gnomAD), exomes 0.00015
Exome Aggregation Consortium (ExAC) 0.00039
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 | ||
---|---|---|---|---|---|---|
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. |
|||
MSH2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
7262 | 7411 |
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. |
---|---|---|---|---|
Conflicting interpretations of pathogenicity (5) |
criteria provided, conflicting classifications
|
Nov 3, 2021 | RCV000034558.23 | |
Likely benign (3) |
reviewed by expert panel
|
Jun 13, 2018 | RCV000076617.10 | |
Likely benign (3) |
criteria provided, multiple submitters, no conflicts
|
Jan 1, 2022 | RCV000115534.14 | |
Likely benign (3) |
criteria provided, multiple submitters, no conflicts
|
Aug 15, 2023 | RCV000202071.14 | |
Likely benign (1) |
criteria provided, single submitter
|
Feb 1, 2018 | RCV000664313.5 | |
Likely benign (1) |
criteria provided, single submitter
|
Jan 31, 2024 | RCV001083980.9 | |
Uncertain significance (1) |
criteria provided, single submitter
|
Jan 1, 2019 | RCV001262884.3 | |
Uncertain significance (1) |
no assertion criteria provided
|
- | RCV001356983.3 | |
Likely benign (1) |
criteria provided, single submitter
|
Jan 28, 2021 | RCV003924894.1 | |
Uncertain significance (1) |
criteria provided, single submitter
|
Oct 8, 2021 | RCV003149608.3 |
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. |
|
---|---|---|---|---|---|
Likely benign
(Jun 13, 2018)
|
reviewed by expert panel
Method: curation
|
Lynch syndrome 1
Affected status: yes
Allele origin:
germline
|
International Society for Gastrointestinal Hereditary Tumours (InSiGHT)
Accession: SCV000107653.5
First in ClinVar: Dec 19, 2013 Last updated: Dec 11, 2022 |
Comment:
Multifactorial likelihood analysis posterior probability < 0.05 (0.006)
|
|
Uncertain significance
(Feb 06, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000884129.1
First in ClinVar: Apr 12, 2013 Last updated: Apr 12, 2013 |
Comment:
The MSH2 c.4G>A; p.Ala2Thr variant (rs63750466) is reported in the literature in multiple individuals with Lynch syndrome (Kurzawski 2006, Mangold 2005a, Mangold 2005b, Nagasaka 2010, … (more)
The MSH2 c.4G>A; p.Ala2Thr variant (rs63750466) is reported in the literature in multiple individuals with Lynch syndrome (Kurzawski 2006, Mangold 2005a, Mangold 2005b, Nagasaka 2010, Pagenstecher 2006, Parc 2003). However, it has been reported to co-occur with a pathogenic MSH2 nonsense variant (Mangold 2005a) and a 3'EPCAM deletion where MSH2 promoter methylation was seen (Nagasaka 2010). This variant is also reported to co-segregate with disease in a large Lynch syndrome family where loss of the MSH2 protein was seen in four individual's tumors; however, RNA analysis showed normal expression, suggesting this variant may be a marker in this family but the functional consequences are uncertain (Pagenstecher 2006). This variant is considered uncertain by an expert review panel in ClinVar (Variation ID: 41650), and is found in the general population with an overall allele frequency of 0.01% (34/241756 alleles) in the Genome Aggregation Database. This variant occurs in a conserved nucleotide of the Kozak consensus sequence, but computational algorithms do not agree as to the effect this variant may have on the protein (SIFT: Tolerated, PolyPhen2: Probably Damaging). Based on available information, the clinical significance of p.Ala2Thr is uncertain at this time. REFERENCES Kurzawski G et al. Germline MSH2 and MLH1 mutational spectrum including large rearrangements in HNPCC families from Poland (update study). Clin Genet. 2006 Jan;69(1):40-7. Mangold E et al. Spectrum and frequencies of mutations in MSH2 and MLH1 identified in 1,721 German families suspected of hereditary nonpolyposis colorectal cancer. Int J Cancer. 2005a Sep 20;116(5):692-702. Mangold E et al. Tumours from MSH2 mutation carriers show loss of MSH2 expression but many tumours from MLH1 mutation carriers exhibit weak positive MLH1 staining. J Pathol. 2005b Dec;207(4):385-95. Nagasaka T et al. Somatic hypermethylation of MSH2 is a frequent event in Lynch Syndrome colorectal cancers. Cancer Res. 2010 Apr 15;70(8):3098-108. Pagenstecher C et al. Aberrant splicing in MLH1 and MSH2 due to exonic and intronic variants. Hum Genet. 2006 Mar;119(1-2):9-22. Parc Y et al. Cancer risk in 348 French MSH2 or MLH1 gene carriers. J Med Genet. 2003 Mar;40(3):208-13. (less)
|
|
Likely benign
(Nov 06, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000149443.15
First in ClinVar: Apr 12, 2013 Last updated: Jul 13, 2019 |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
|
|
Likely benign
(May 03, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000696273.3
First in ClinVar: Apr 12, 2013 Last updated: Jul 28, 2019 |
Comment:
Variant summary: MSH2 c.4G>A (p.Ala2Thr) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging … (more)
Variant summary: MSH2 c.4G>A (p.Ala2Thr) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. 5/5 computational tools predict no significant impact on normal splicing. This was confirmed by RT-PCR results (Pagenstecher_2006). The variant allele was found at a frequency of 0.00016 in 217422 control chromosomes (gnomAD and publication data). This frequency is not significantly higher than expected for a pathogenic variant in MSH2 causing Lynch Syndrome (0.00016 vs 0.00057), allowing no conclusion about variant significance. The variant, c.4G>A, has been reported in the literature in individuals affected with Lynch Syndrome, uveal malignant melanoma or autosomal dominant cancer predisposition syndromes (Mangold_2005, Kurzawski_2006, Schrader_2016, Bonadona_2011, Hajkova_2018, Zhang_2015). One publication reported one family where it showed segregation of this variant with Lynch syndrome (Mangold_2005). However, in many reports, not all MMR genes were tested or MLPA applied. Consequently, these reports do not provide unequivocal conclusions about association of the variant with Lynch Syndrome. Furthermore, in some of these families co-occurrences with other pathogenic variants have been reported (MSH2 c.1835C>G, p.Ser612X (Mangold_2005); EPCAM deletion associated with MSH2 promoter methylation (Nagasaka_2010); MSH2 c.1delA (UMD); RAD51C c.97C>T, p.Gln33X (Internal database)), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six clinical diagnostic laboratories and one expert panel (InSiGHT) have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (Likely benign (n=4 to include the expert panel), VUS (n=3)). Based on the evidence outlined above, the variant was classified as likely benign. (less)
|
|
Likely benign
(Apr 09, 2021)
|
criteria provided, single submitter
Method: curation
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Sema4, Sema4
Accession: SCV002534527.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022 |
|
|
Likely benign
(Jan 28, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
MSH2-related condition
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV004744178.1
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).
|
|
Likely benign
(Feb 01, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary nonpolyposis colon cancer
(Autosomal dominant inheritance)
Affected status: no
Allele origin:
germline
|
University of Washington Department of Laboratory Medicine, University of Washington
Accession: SCV000788246.1
First in ClinVar: Jul 28, 2018 Last updated: Jul 28, 2018 |
Comment:
MSH2 p.A2T has been reported to co-occur with a MSH2 nonsense variant and a 3' EPCAM deletion where MSH2 promoter methylation was identified (Mangold 2005, … (more)
MSH2 p.A2T has been reported to co-occur with a MSH2 nonsense variant and a 3' EPCAM deletion where MSH2 promoter methylation was identified (Mangold 2005, Nagasaka 2010). Functional RNA studies performed on peripheral blood found normal RNA levels in patients that carry p.A2T (Pagenstecher 2006). MSH2 p.A2T was observed at an allele frequency of 0.0724% (14/19320 alleles) in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016), and it was observed in 1/208 individuals with atherosclerosis, with no specific information about cancer history (Johnston 2012). (less)
Clinical Features:
Colon cancer (present) , Colorectal polyps (present)
|
|
Uncertain significance
(Jan 01, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Breast carcinoma
Affected status: yes
Allele origin:
unknown
|
Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV001440919.1
First in ClinVar: Oct 31, 2020 Last updated: Oct 31, 2020 |
|
|
Likely benign
(Sep 24, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000184713.8
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
|
|
Uncertain significance
(Jul 05, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Lynch syndrome 1
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000488838.2
First in ClinVar: Jan 31, 2016 Last updated: Dec 24, 2022 |
|
|
Uncertain significance
(Oct 08, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Breast and/or ovarian cancer
Affected status: unknown
Allele origin:
germline
|
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
Accession: SCV003838426.1
First in ClinVar: Mar 11, 2023 Last updated: Mar 11, 2023 |
|
|
Uncertain significance
(Nov 03, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: not provided
Allele origin:
germline
|
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden
Accession: SCV002009326.3
First in ClinVar: Nov 05, 2021 Last updated: Jul 16, 2023 |
|
|
Benign
(Mar 24, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Lynch syndrome 1
Affected status: unknown
Allele origin:
unknown
|
Myriad Genetics, Inc.
Accession: SCV004018428.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023 |
Comment:
This variant is considered benign. This variant has been observed in trans with a known pathogenic variant in one or more individuals lacking clinical features … (more)
This variant is considered benign. This variant has been observed in trans with a known pathogenic variant in one or more individuals lacking clinical features consistent with gene-specific recessive disease. This variant is strongly associated with less severe personal and family histories of cancer, typical for individuals without pathogenic variants in this gene [PMID: 25085752]. (less)
|
|
Likely benign
(Aug 15, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV002552181.4
First in ClinVar: Jul 27, 2022 Last updated: Aug 18, 2023 |
|
|
Likely benign
(Aug 09, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
unknown
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV001134367.5
First in ClinVar: Jan 05, 2020 Last updated: Jan 06, 2024 |
|
|
Likely benign
(Jan 31, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary nonpolyposis colorectal neoplasms
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV000259383.11
First in ClinVar: Jan 31, 2016 Last updated: Feb 14, 2024 |
|
|
Likely benign
(Jan 01, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000902739.2
First in ClinVar: May 19, 2019 Last updated: Feb 14, 2024 |
|
|
Uncertain significance
(-)
|
no assertion criteria provided
Method: research
|
not specified
Affected status: unknown
Allele origin:
unknown
|
Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV000257190.1
First in ClinVar: Nov 20, 2015 Last updated: Nov 20, 2015 |
Number of individuals with the variant: 1
|
|
variant of unknown significance
(Jul 13, 2012)
|
no assertion criteria provided
Method: research
|
not provided
Affected status: no
Allele origin:
germline
|
Biesecker Lab/Clinical Genomics Section, National Institutes of Health
Study: ClinSeq
Accession: SCV000043334.1 First in ClinVar: Apr 12, 2013 Last updated: Apr 12, 2013 |
Comment:
Converted during submission to Uncertain significance.
Number of individuals with the variant: 1
Comment on evidence:
The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:22703879 for … (more)
The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:22703879 for details. (less)
|
|
Uncertain significance
(-)
|
no assertion criteria provided
Method: clinical testing
|
Malignant tumor of breast
Affected status: yes
Allele origin:
unknown
|
Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV001552292.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021 |
Comment:
The MSH2 p.Ala2Thr variant was identified in 15 of 38724 proband chromosomes (frequency: 0.0004) from individuals or families with lynch syndrome or colorectal cancer (Bonadona … (more)
The MSH2 p.Ala2Thr variant was identified in 15 of 38724 proband chromosomes (frequency: 0.0004) from individuals or families with lynch syndrome or colorectal cancer (Bonadona 2011, Dymerska 2010, Johnston 2012, Kurzawski 2006, Mangold 2005, Nagasaka 2010, Parc 2003). The variant was identified in dbSNP (ID: rs63750466) as “With Uncertain significance allele”, ClinVar (as uncertain significance, reviewed by an expert panel including 6x as uncertain significance and 2x as likely benign), Clinvitae (5x), UMD-LSDB (30x as neutral), Mismatch Repair Genes Variant Database, and in the Insight Hereditary Tumors database (19x). In UMD the variant was identified with a co-occurring pathogenic MSH2 variant (c.1delA, p.Met1?), increasing the likelihood that the p.Ala2Thr variant does not have clinical significance. The variant was not identified in the COGR, Cosmic, MutDB, or Zhejiang University databases. The variant was identified in control databases in 34 of 241756 chromosomes at a frequency of 0.0001 (Genome Aggregation Database Feb 27, 2017). It was observed in the following populations: “Other” in 1 of 5740 chromosomes (freq: 0.0002), European in 25 of 109176 chromosomes (freq: 0.0002), and Finnish in 8 of 21430 chromosomes (freq: 0.0004); it was not observed in the African, Latino, Ashkenazi Jewish, East Asian, or South Asian populations. The p.Ala2 residue is conserved across mammals and other organisms, and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest that the variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. The variant occurs outside of the splicing consensus sequence and 1 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In one study, Immunohistochemical analysis of this variant in tumors from relatives (mother and son - both of whom were carriers of the variant) revealed a loss of MSH2 protein expression; this finding supported a pathogenic role for the MSH2, c.4G>A, p.Ala2Thr variant (Mangold 2005). In another publication this variant is reported to segregate with the disease in several family members (at least 10 meioses) and showed loss of MSH2 expression in tumors of four affected family members. This variant is clearly linked to the disease in this specific family (Pagenstecher 2006). However, there is conflicting evidence in the literature; this variant was identified in an individual as co-occurring with pathogenic variant in MSH2 (c.1835C>G, p.S612X) (Lucci-Cordisco 2006, Mangold 2005). In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. (less)
|
|
click to load more click to collapse |
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 |
---|---|---|---|---|
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 |
The Frequency of Discordant Variant Classification in the Human Gene Mutation Database: A Comparison of the American College of Medical Genetics and Genomics Guidelines and ClinVar. | Park KJ | Laboratory medicine | 2021 | PMID: 32926152 |
Methylation Tolerance-Based Functional Assay to Assess Variants of Unknown Significance in the MLH1 and MSH2 Genes and Identify Patients With Lynch Syndrome. | Bouvet D | Gastroenterology | 2019 | PMID: 30998989 |
Elucidating the role of interacting residues of the MSH2-MSH6 complex in DNA repair mechanism: A computational approach. | Thirumal Kumar D | Advances in protein chemistry and structural biology | 2019 | PMID: 30798936 |
Germline mutation in the TP53 gene in uveal melanoma. | Hajkova N | Scientific reports | 2018 | PMID: 29769598 |
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 |
Germline Variants in Targeted Tumor Sequencing Using Matched Normal DNA. | Schrader KA | JAMA oncology | 2016 | PMID: 26556299 |
Clinicopathologic, molecular, and prognostic implications of the loss of EPCAM expression in colorectal carcinoma. | Kim JH | Oncotarget | 2016 | PMID: 26528695 |
Germline Mutations in Predisposition Genes in Pediatric Cancer. | Zhang J | The New England journal of medicine | 2015 | PMID: 26580448 |
Identification of a Variety of Mutations in Cancer Predisposition Genes in Patients With Suspected Lynch Syndrome. | Yurgelun MB | Gastroenterology | 2015 | PMID: 25980754 |
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. | Richards S | Genetics in medicine : official journal of the American College of Medical Genetics | 2015 | PMID: 25741868 |
Development and validation of a new algorithm for the reclassification of genetic variants identified in the BRCA1 and BRCA2 genes. | Pruss D | Breast cancer research and treatment | 2014 | PMID: 25085752 |
Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database. | Thompson BA | Nature genetics | 2014 | PMID: 24362816 |
Calibration of multiple in silico tools for predicting pathogenicity of mismatch repair gene missense substitutions. | Thompson BA | Human mutation | 2013 | PMID: 22949387 |
Secondary variants in individuals undergoing exome sequencing: screening of 572 individuals identifies high-penetrance mutations in cancer-susceptibility genes. | Johnston JJ | American journal of human genetics | 2012 | PMID: 22703879 |
Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome. | Bonadona V | JAMA | 2011 | PMID: 21642682 |
Somatic hypermethylation of MSH2 is a frequent event in Lynch Syndrome colorectal cancers. | Nagasaka T | Cancer research | 2010 | PMID: 20388775 |
Combined iPLEX and TaqMan assays to screen for 45 common mutations in Lynch syndrome and FAP patients. | Dymerska D | The Journal of molecular diagnostics : JMD | 2010 | PMID: 20007843 |
The use of microsatellite instability, immunohistochemistry and other variables in determining the clinical significance of MLH1 and MSH2 unclassified variants in Lynch syndrome. | Lucci-Cordisco E | Cancer biomarkers : section A of Disease markers | 2006 | PMID: 17192056 |
Identification of mismatch repair gene mutations in young patients with colorectal cancer and in patients with multiple tumours associated with hereditary non-polyposis colorectal cancer. | Niessen RC | Gut | 2006 | PMID: 16636019 |
Germline MSH2 and MLH1 mutational spectrum including large rearrangements in HNPCC families from Poland (update study). | Kurzawski G | Clinical genetics | 2006 | PMID: 16451135 |
Aberrant splicing in MLH1 and MSH2 due to exonic and intronic variants. | Pagenstecher C | Human genetics | 2006 | PMID: 16341550 |
Tumours from MSH2 mutation carriers show loss of MSH2 expression but many tumours from MLH1 mutation carriers exhibit weak positive MLH1 staining. | Mangold E | The Journal of pathology | 2005 | PMID: 16216036 |
Spectrum and frequencies of mutations in MSH2 and MLH1 identified in 1,721 German families suspected of hereditary nonpolyposis colorectal cancer. | Mangold E | International journal of cancer | 2005 | PMID: 15849733 |
Cancer risk in 348 French MSH2 or MLH1 gene carriers. | Parc Y | Journal of medical genetics | 2003 | PMID: 12624141 |
http://www.insight-database.org/classifications/?gene=MSH2&variant=c.4G%3EA | - | - | - | - |
http://www.insight-database.org/classifications/index.html?gene=MSH2&variant=c.4G%3EA | - | - | - | - |
click to load more click to collapse |
Text-mined citations for rs63750466 ...
HelpRecord last updated Mar 17, 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.