The c.756_761delAGATTC variant (also known as p.D253_S254del) is located in coding exon 4 of the MSH6 gene. This variant results from an in-frame AGATTC deletion at nucleotide positions 756 to 761. This results in the in-frame deletion of an aspartic acid and a serine at codon 253 to 254. This amino acid region is generally well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
ClinVar Genomic variation as it relates to human health
NM_000179.3(MSH6):c.756_761del (p.Asp253_Ser254del)
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)
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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.
Uncertain significance
1
criteria provided, single submitter
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000179.3(MSH6):c.756_761del (p.Asp253_Ser254del)
Variation ID: 2567481 Accession: VCV002567481.2
- Type and length
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Deletion, 6 bp
- Location
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Cytogenetic: 2p16.3 2: 47798737-47798742 (GRCh38) [ NCBI UCSC ] 2: 48025876-48025881 (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 Jul 8, 2023 May 1, 2024 May 25, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000179.3:c.756_761del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000170.1:p.Asp253_Ser254del inframe deletion NM_001281492.2:c.366_371del NP_001268421.1:p.Asp123_Ser124del inframe deletion NM_001281493.2:c.-151_-146del 5 prime UTR NM_001281494.2:c.-151_-146del 5 prime UTR NM_001406795.1:c.852_857del NP_001393724.1:p.Asp285_Ser286del inframe deletion NM_001406796.1:c.756_761del NP_001393725.1:p.Asp253_Ser254del inframe deletion NM_001406797.1:c.459_464del NP_001393726.1:p.Asp154_Ser155del inframe deletion NM_001406798.1:c.756_761del NP_001393727.1:p.Asp253_Ser254del inframe deletion NM_001406799.1:c.231_236del NP_001393728.1:p.Asp78_Ser79del inframe deletion NM_001406800.1:c.756_761del NP_001393729.1:p.Asp253_Ser254del inframe deletion NM_001406801.1:c.459_464del NP_001393730.1:p.Asp154_Ser155del inframe deletion NM_001406802.1:c.852_857del NP_001393731.1:p.Asp285_Ser286del inframe deletion NM_001406803.1:c.756_761del NP_001393732.1:p.Asp253_Ser254del inframe deletion NM_001406804.1:c.678_683del NP_001393733.1:p.Asp227_Ser228del inframe deletion NM_001406805.1:c.459_464del NP_001393734.1:p.Asp154_Ser155del inframe deletion NM_001406806.1:c.231_236del NP_001393735.1:p.Asp78_Ser79del inframe deletion NM_001406807.1:c.231_236del NP_001393736.1:p.Asp78_Ser79del inframe deletion NM_001406808.1:c.756_761del NP_001393737.1:p.Asp253_Ser254del inframe deletion NM_001406809.1:c.756_761del NP_001393738.1:p.Asp253_Ser254del inframe deletion NM_001406811.1:c.-151_-146del 5 prime UTR NM_001406812.1:c.-151_-146del 5 prime UTR NM_001406813.1:c.762_767del NP_001393742.1:p.Asp255_Ser256del inframe deletion NM_001406814.1:c.-151_-146del 5 prime UTR NM_001406815.1:c.-151_-146del 5 prime UTR NM_001406816.1:c.-151_-146del 5 prime UTR NM_001406817.1:c.756_761del NP_001393746.1:p.Asp253_Ser254del inframe deletion NM_001406818.1:c.459_464del NP_001393747.1:p.Asp154_Ser155del inframe deletion NM_001406819.1:c.459_464del NP_001393748.1:p.Asp154_Ser155del inframe deletion NM_001406820.1:c.459_464del NP_001393749.1:p.Asp154_Ser155del inframe deletion NM_001406821.1:c.459_464del NP_001393750.1:p.Asp154_Ser155del inframe deletion NM_001406822.1:c.459_464del NP_001393751.1:p.Asp154_Ser155del inframe deletion NM_001406823.1:c.-151_-146del 5 prime UTR NM_001406824.1:c.459_464del NP_001393753.1:p.Asp154_Ser155del inframe deletion NM_001406825.1:c.459_464del NP_001393754.1:p.Asp154_Ser155del inframe deletion NM_001406826.1:c.588_593del NP_001393755.1:p.Asp197_Ser198del inframe deletion NM_001406827.1:c.459_464del NP_001393756.1:p.Asp154_Ser155del inframe deletion NM_001406828.1:c.459_464del NP_001393757.1:p.Asp154_Ser155del inframe deletion NM_001406829.1:c.-151_-146del 5 prime UTR NM_001406830.1:c.459_464del NP_001393759.1:p.Asp154_Ser155del inframe deletion NM_001407362.1:c.628-1927_628-1922del intron variant NR_176257.1:n.845_850del non-coding transcript variant NR_176258.1:n.845_850del non-coding transcript variant NR_176259.1:n.845_850del non-coding transcript variant NR_176261.1:n.845_850del non-coding transcript variant NC_000002.12:g.47798739_47798744del NC_000002.11:g.48025878_48025883del NG_007111.1:g.20593_20598del LRG_219:g.20593_20598del LRG_219t1:c.756_761del LRG_219p1:p.Asp253_Ser254del - Protein change
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- Other names
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- Canonical SPDI
- NC_000002.12:47798736:TCAGATTC:TC
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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.
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- 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. |
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| MSH6 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
9158 | 9474 | |
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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| Uncertain significance (1) |
criteria provided, single submitter
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May 25, 2023 | RCV003311263.2 |
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. |
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Uncertain significance
(May 25, 2023)
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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: SCV004007736.2
First in ClinVar: Jul 08, 2023 Last updated: May 01, 2024 |
Comment:
The c.756_761delAGATTC variant (also known as p.D253_S254del) is located in coding exon 4 of the MSH6 gene. This variant results from an in-frame AGATTC deletion … (more)
The c.756_761delAGATTC variant (also known as p.D253_S254del) is located in coding exon 4 of the MSH6 gene. This variant results from an in-frame AGATTC deletion at nucleotide positions 756 to 761. This results in the in-frame deletion of an aspartic acid and a serine at codon 253 to 254. This amino acid region is generally well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (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.756_761delAGATTC variant (also known as p.D253_S254del) is located in coding exon 4 of the MSH6 gene. This variant results from an in-frame AGATTC deletion at nucleotide positions 756 to 761. This results in the in-frame deletion of an aspartic acid and a serine at codon 253 to 254. This amino acid region is generally well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Citations for germline classification of this variant
Help| There 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.