ClinVar Genomic variation as it relates to human health
NM_001048174.2(MUTYH):c.1392_1392+6del
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_001048174.2(MUTYH):c.1392_1392+6del
Variation ID: 182684 Accession: VCV000182684.16
- Type and length
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Deletion, 7 bp
- Location
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Cytogenetic: 1p34.1 1: 45331176-45331182 (GRCh38) [ NCBI UCSC ] 1: 45796848-45796854 (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 Dec 19, 2017 May 1, 2024 Jan 2, 2024 - HGVS
- ... more HGVS ... less HGVS
- Protein change
- Other names
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- Canonical SPDI
- NC_000001.11:45331175:TAGTGCCT:T
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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
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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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
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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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MUTYH | - | - |
GRCh38 GRCh37 |
2686 | 2842 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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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 pathogenic (1) |
criteria provided, single submitter
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Sep 18, 2018 | RCV000160747.4 | |
Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Mar 1, 2023 | RCV000215481.10 | |
Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Jan 2, 2024 | RCV001781503.7 |
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
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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 pathogenic
(Apr 14, 2023)
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criteria provided, single submitter
Method: clinical testing
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Familial adenomatous polyposis 2
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004198972.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Likely pathogenic
(Mar 01, 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: SCV000272960.8
First in ClinVar: May 29, 2016 Last updated: May 01, 2024 |
Comment:
The c.1476_1476+6delGGCACTA variant, located in coding exon and intron 14 of the MUTYH gene, results from a deletion of the last nucleotide of exon 14 … (more)
The c.1476_1476+6delGGCACTA variant, located in coding exon and intron 14 of the MUTYH gene, results from a deletion of the last nucleotide of exon 14 and six nucleotides of the adjacent intron, which includes the canonical splice donor site. Alterations that disrupt the canonical splice site are expected to result in aberrant splicing. The resulting transcript is predicted to be in-frame and is not expected to trigger nonsense-mediated mRNAdecay. The exact functional effect of the altered amino acid sequence is unknown; however, the impacted region is critical for protein function (Ambry internal data). RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). The canonical splice donor site is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. Based on the majority of available evidence to date, this variant is likely to be pathogenic. (less)
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Likely pathogenic
(Jun 30, 2019)
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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: SCV000685585.3
First in ClinVar: Feb 19, 2018 Last updated: Jan 12, 2022 |
Comment:
This variant deletes 7 nucleotides in the exon 14/intron 14 splice junction of the MUTYH gene, removing the splice donor site. Aberrant splicing is expected … (more)
This variant deletes 7 nucleotides in the exon 14/intron 14 splice junction of the MUTYH gene, removing the splice donor site. Aberrant splicing is expected to result in a premature translation stop signal and an absent or non-functional protein product, but this has not been tested experimentally. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of MUTYH function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Likely Pathogenic. (less)
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Likely pathogenic
(Sep 18, 2018)
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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: SCV000211391.11
First in ClinVar: Feb 24, 2015 Last updated: Dec 19, 2017 |
Comment:
This deletion of 7 nucleotides in MUTYH is denoted c.1476_1476+6delGGCACTA at the cDNA level. The normal sequence, with the bases that are deleted in brackets, … (more)
This deletion of 7 nucleotides in MUTYH is denoted c.1476_1476+6delGGCACTA at the cDNA level. The normal sequence, with the bases that are deleted in brackets, is GAAAAA[delGgcacta]cctt, where the capital letters are exonic and lowercase are intronic. The deletion spans the intron/exon boundary, removing the canonical splice donor site. It is predicted to cause abnormal gene splicing, leading to either an abnormal message that is subject to nonsense-mediated mRNA decay or to an abnormal protein product. Although this variant has not, to our knowledge, been reported in the literature, it is considered likely pathogenic. (less)
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Likely pathogenic
(Jan 02, 2024)
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criteria provided, single submitter
Method: clinical testing
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Familial adenomatous polyposis 2
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV002294442.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 20, 2024 |
Comment:
This variant results in the deletion of intron 14 of the MUTYH gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor … (more)
This variant results in the deletion of intron 14 of the MUTYH gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MUTYH are known to be pathogenic (PMID: 18534194, 20663686). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MUTYH-related conditions. ClinVar contains an entry for this variant (Variation ID: 182684). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. (less)
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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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MUTYH-associated polyposis (MAP). | Nielsen M | Critical reviews in oncology/hematology | 2011 | PMID: 20663686 |
Characterization of mutant MUTYH proteins associated with familial colorectal cancer. | Ali M | Gastroenterology | 2008 | PMID: 18534194 |
Splicing in action: assessing disease causing sequence changes. | Baralle D | Journal of medical genetics | 2005 | PMID: 16199547 |
Text-mined citations for rs864621967 ...
HelpRecord last updated Sep 29, 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.