The c.1721delA pathogenic mutation, located in coding exon 11 of the MSH2 gene, results from a deletion of one nucleotide at nucleotide position 1721, causing a translational frameshift with a predicted alternate stop codon (p.Q574Rfs*16). A different single nucleotide deletion (c.1720delC) resulting in the same frameshift alteration (p.Q574Rfs*16) was identified in 1/454 unrelated German patients with suspected HNPCC (Mangold E et al. Int. J. Cancer 2005 Sep;116:692-702). 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.
ClinVar Genomic variation as it relates to human health
NM_000251.3(MSH2):c.1721del (p.Gln574fs)
Germline
Classification
Help
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.
(1)
Help
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.
Pathogenic
1
criteria provided, single submitter
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000251.3(MSH2):c.1721del (p.Gln574fs)
Variation ID: 1778773 Accession: VCV001778773.2
- Type and length
-
Deletion, 1 bp
- Location
-
Cytogenetic: 2p21 2: 47471024 (GRCh38) [ NCBI UCSC ] 2: 47698163 (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 Nov 28, 2017 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000251.3:c.1721del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000242.1:p.Gln574fs frameshift NM_001258281.1:c.1523del NP_001245210.1:p.Gln508fs frameshift NM_001406631.1:c.1721delA NP_001393560.1:p.Gln574Argfs frameshift NM_001406632.1:c.1721delA NP_001393561.1:p.Gln574Argfs frameshift NM_001406633.1:c.1721delA NP_001393562.1:p.Gln574Argfs frameshift NM_001406634.1:c.1721delA NP_001393563.1:p.Gln574Argfs frameshift NM_001406635.1:c.1721delA NP_001393564.1:p.Gln574Argfs frameshift NM_001406636.1:c.1688delA NP_001393565.1:p.Gln563Argfs frameshift NM_001406637.1:c.1721delA NP_001393566.1:p.Gln574Argfs frameshift NM_001406638.1:c.1760delA NP_001393567.1:p.Gln587Argfs frameshift NM_001406639.1:c.1721delA NP_001393568.1:p.Gln574Argfs frameshift NM_001406640.1:c.1721delA NP_001393569.1:p.Gln574Argfs frameshift NM_001406641.1:c.1721delA NP_001393570.1:p.Gln574Argfs frameshift NM_001406642.1:c.1721delA NP_001393571.1:p.Gln574Argfs frameshift NM_001406643.1:c.1721delA NP_001393572.1:p.Gln574Argfs frameshift NM_001406644.1:c.1721delA NP_001393573.1:p.Gln574Argfs frameshift NM_001406645.1:c.1721delA NP_001393574.1:p.Gln574Argfs frameshift NM_001406646.1:c.1721delA NP_001393575.1:p.Gln574Argfs frameshift NM_001406647.1:c.1571delA NP_001393576.1:p.Gln524Argfs frameshift NM_001406648.1:c.1721delA NP_001393577.1:p.Gln574Argfs frameshift NM_001406649.1:c.1571delA NP_001393578.1:p.Gln524Argfs frameshift NM_001406650.1:c.1571delA NP_001393579.1:p.Gln524Argfs frameshift NM_001406651.1:c.1571delA NP_001393580.1:p.Gln524Argfs frameshift NM_001406652.1:c.1571delA NP_001393581.1:p.Gln524Argfs frameshift NM_001406653.1:c.1661delA NP_001393582.1:p.Gln554Argfs frameshift NM_001406654.1:c.1301delA NP_001393583.1:p.Gln434Argfs frameshift NM_001406655.1:c.1721delA NP_001393584.1:p.Gln574Argfs frameshift NM_001406656.1:c.824delA NP_001393585.1:p.Gln275Argfs frameshift NM_001406658.1:c.365delA NP_001393587.1:p.Gln122Argfs frameshift NM_001406659.1:c.365delA NP_001393588.1:p.Gln122Argfs frameshift NM_001406660.1:c.365delA NP_001393589.1:p.Gln122Argfs frameshift NM_001406661.1:c.365delA NP_001393590.1:p.Gln122Argfs frameshift NM_001406662.1:c.365delA NP_001393591.1:p.Gln122Argfs frameshift NM_001406669.1:c.365delA NP_001393598.1:p.Gln122Argfs frameshift NM_001406674.1:c.1721delA NP_001393603.1:p.Gln574Argfs frameshift NR_176230.1:n.1757delA NR_176231.1:n.1757delA NR_176232.1:n.1757delA NR_176233.1:n.1599delA NR_176234.1:n.1757delA NR_176235.1:n.1757delA NR_176236.1:n.1757delA NR_176237.1:n.1757delA NR_176238.1:n.1890delA NR_176239.1:n.1757delA NR_176240.1:n.1757delA NR_176241.1:n.1757delA NR_176242.1:n.1757delA NR_176243.1:n.1607delA NR_176244.1:n.1757delA NR_176245.1:n.1757delA NR_176246.1:n.1757delA NR_176247.1:n.1757delA NR_176248.1:n.1757delA NR_176249.1:n.1987delA NR_176250.1:n.1497delA NC_000002.12:g.47471024del NC_000002.11:g.47698163del NG_007110.2:g.72901del LRG_218:g.72901del LRG_218t1:c.1721del LRG_218p1:p.Gln574Argfs - Protein change
- Q574fs, Q508fs
- Other names
- -
- Canonical SPDI
- NC_000002.12:47471023: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.
- -
- 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 |
7404 | 7566 | |
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
|
Nov 28, 2017 | RCV002399065.2 |
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
(Nov 28, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV002713641.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The c.1721delA pathogenic mutation, located in coding exon 11 of the MSH2 gene, results from a deletion of one nucleotide at nucleotide position 1721, causing … (more)
The c.1721delA pathogenic mutation, located in coding exon 11 of the MSH2 gene, results from a deletion of one nucleotide at nucleotide position 1721, causing a translational frameshift with a predicted alternate stop codon (p.Q574Rfs*16). A different single nucleotide deletion (c.1720delC) resulting in the same frameshift alteration (p.Q574Rfs*16) was identified in 1/454 unrelated German patients with suspected HNPCC (Mangold E et al. Int. J. Cancer 2005 Sep;116:692-702). 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)
|
Comment:
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. |
Comment:
The c.1721delA pathogenic mutation, located in coding exon 11 of the MSH2 gene, results from a deletion of one nucleotide at nucleotide position 1721, causing a translational frameshift with a predicted alternate stop codon (p.Q574Rfs*16). A different single nucleotide deletion (c.1720delC) resulting in the same frameshift alteration (p.Q574Rfs*16) was identified in 1/454 unrelated German patients with suspected HNPCC (Mangold E et al. Int. J. Cancer 2005 Sep;116:692-702). 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.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| 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 |
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.