ClinVar Genomic variation as it relates to human health
NM_000251.3(MSH2):c.1856_1857insG (p.Tyr619Ter)
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.1856_1857insG (p.Tyr619Ter)
Variation ID: 1781399 Accession: VCV001781399.2
- Type and length
-
Insertion, 1 bp
- Location
-
Cytogenetic: 2p21 2: 47475121-47475122 (GRCh38) [ NCBI UCSC ] 2: 47702260-47702261 (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 Nov 29, 2022 May 1, 2024 May 4, 2020 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_000251.3:c.1856_1857insG MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000242.1:p.Tyr619Ter nonsense NM_001258281.1:c.1658_1659insG NP_001245210.1:p.Tyr553Ter nonsense NM_001406631.1:c.1856_1857insG NP_001393560.1:p.Tyr619Terfs frameshift nonsense NM_001406632.1:c.1856_1857insG NP_001393561.1:p.Tyr619Terfs frameshift nonsense NM_001406633.1:c.1856_1857insG NP_001393562.1:p.Tyr619Terfs frameshift nonsense NM_001406634.1:c.1856_1857insG NP_001393563.1:p.Tyr619Terfs frameshift nonsense NM_001406635.1:c.1856_1857insG NP_001393564.1:p.Tyr619Terfs frameshift nonsense NM_001406636.1:c.1823_1824insG NP_001393565.1:p.Tyr608Terfs frameshift nonsense NM_001406637.1:c.1856_1857insG NP_001393566.1:p.Tyr619Terfs frameshift nonsense NM_001406638.1:c.1895_1896insG NP_001393567.1:p.Tyr632Terfs frameshift nonsense NM_001406639.1:c.1856_1857insG NP_001393568.1:p.Tyr619Terfs frameshift nonsense NM_001406640.1:c.1856_1857insG NP_001393569.1:p.Tyr619Terfs frameshift nonsense NM_001406641.1:c.1856_1857insG NP_001393570.1:p.Tyr619Terfs frameshift nonsense NM_001406642.1:c.1856_1857insG NP_001393571.1:p.Tyr619Terfs frameshift nonsense NM_001406643.1:c.1856_1857insG NP_001393572.1:p.Tyr619Terfs frameshift nonsense NM_001406644.1:c.1856_1857insG NP_001393573.1:p.Tyr619Terfs frameshift nonsense NM_001406645.1:c.1856_1857insG NP_001393574.1:p.Tyr619Terfs frameshift nonsense NM_001406646.1:c.1856_1857insG NP_001393575.1:p.Tyr619Terfs frameshift nonsense NM_001406647.1:c.1706_1707insG NP_001393576.1:p.Tyr569Terfs frameshift nonsense NM_001406648.1:c.1856_1857insG NP_001393577.1:p.Tyr619Terfs frameshift nonsense NM_001406649.1:c.1706_1707insG NP_001393578.1:p.Tyr569Terfs frameshift nonsense NM_001406650.1:c.1706_1707insG NP_001393579.1:p.Tyr569Terfs frameshift nonsense NM_001406651.1:c.1706_1707insG NP_001393580.1:p.Tyr569Terfs frameshift nonsense NM_001406652.1:c.1706_1707insG NP_001393581.1:p.Tyr569Terfs frameshift nonsense NM_001406653.1:c.1796_1797insG NP_001393582.1:p.Tyr599Terfs frameshift nonsense NM_001406654.1:c.1436_1437insG NP_001393583.1:p.Tyr479Terfs frameshift nonsense NM_001406655.1:c.1856_1857insG NP_001393584.1:p.Tyr619Terfs frameshift nonsense NM_001406656.1:c.959_960insG NP_001393585.1:p.Tyr320Terfs frameshift nonsense NM_001406657.1:c.*66_*67insG NM_001406658.1:c.500_501insG NP_001393587.1:p.Tyr167Terfs frameshift nonsense NM_001406659.1:c.500_501insG NP_001393588.1:p.Tyr167Terfs frameshift nonsense NM_001406660.1:c.500_501insG NP_001393589.1:p.Tyr167Terfs frameshift nonsense NM_001406661.1:c.500_501insG NP_001393590.1:p.Tyr167Terfs frameshift nonsense NM_001406662.1:c.500_501insG NP_001393591.1:p.Tyr167Terfs frameshift nonsense NM_001406669.1:c.500_501insG NP_001393598.1:p.Tyr167Terfs frameshift nonsense NM_001406674.1:c.1856_1857insG NP_001393603.1:p.Tyr619Terfs frameshift nonsense NR_176230.1:n.1892_1893insG NR_176231.1:n.1892_1893insG NR_176232.1:n.1892_1893insG NR_176233.1:n.1734_1735insG NR_176234.1:n.1892_1893insG NR_176235.1:n.1892_1893insG NR_176236.1:n.1892_1893insG NR_176237.1:n.1892_1893insG NR_176238.1:n.2025_2026insG NR_176239.1:n.1892_1893insG NR_176240.1:n.1892_1893insG NR_176241.1:n.1892_1893insG NR_176242.1:n.1892_1893insG NR_176243.1:n.1742_1743insG NR_176244.1:n.1892_1893insG NR_176245.1:n.1892_1893insG NR_176246.1:n.1892_1893insG NR_176247.1:n.1892_1893insG NR_176248.1:n.1892_1893insG NR_176249.1:n.2122_2123insG NR_176250.1:n.1632_1633insG NC_000002.12:g.47475121_47475122insG NC_000002.11:g.47702260_47702261insG NG_007110.2:g.76998_76999insG LRG_218:g.76998_76999insG LRG_218t1:c.1856_1857insG LRG_218p1:p.Tyr619Terfs - Protein change
- Y553*, Y619*
- Other names
- -
- Canonical SPDI
- NC_000002.12:47475121::G
-
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.
-
- Links
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 |
7401 | 7563 |
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. |
---|---|---|---|---|
Pathogenic (1) |
criteria provided, single submitter
|
May 4, 2020 | RCV002413086.2 |
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. |
|
---|---|---|---|---|---|
Pathogenic
(May 04, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV002722108.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The c.1856_1857insG pathogenic mutation, located in coding exon 12 of the MSH2 gene, results from an insertion of one nucleotide at position 1856, causing a … (more)
The c.1856_1857insG pathogenic mutation, located in coding exon 12 of the MSH2 gene, results from an insertion of one nucleotide at position 1856, causing a translational frameshift with a predicted alternate stop codon (p.Y619*). A different alteration that results in a stop codon at the same amino acid position, c.1857T>G, has been reported in multiple individuals that meet Amsterdam criteria for Lynch syndrome and one individual with MSI-H colon cancer that displayed absent MSH2 staining on immunohistochemistry (IHC) (Lu SL et al. Jpn. J. Cancer Res., 1996 Mar;87:279-87; Bai YQ et al. Int. J. Cancer, 1999 Aug;82:512-5; Krüger S et al. Hum. Mutat., 2002 Jan;19:82). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (less)
|
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
HelpThere are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
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.