ClinVar Genomic variation as it relates to human health
NM_004006.3(DMD):c.1812+1G>A
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_004006.3(DMD):c.1812+1G>A
Variation ID: 162497 Accession: VCV000162497.35
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: Xp21.1 X: 32573529 (GRCh38) [ NCBI UCSC ] X: 32591646 (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 Jan 18, 2015 May 12, 2024 Dec 22, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_004006.3:c.1812+1G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
splice donor NM_000109.4:c.1788+1G>A splice donor NM_004009.3:c.1800+1G>A splice donor NM_004010.3:c.1443+1G>A splice donor NC_000023.11:g.32573529C>T NC_000023.10:g.32591646C>T NG_012232.1:g.771081G>A LRG_199:g.771081G>A LRG_199t1:c.1812+1G>A - Protein change
- Other names
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- Canonical SPDI
- NC_000023.11:32573528:C: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
Help
The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.00003
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00009
Exome Aggregation Consortium (ExAC) 0.00002
The Genome Aggregation Database (gnomAD), exomes 0.00002
The Genome Aggregation Database (gnomAD) 0.00003
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 | ||
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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
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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DMD | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
9077 | 9365 |
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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Pathogenic/Likely pathogenic (5) |
criteria provided, multiple submitters, no conflicts
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Apr 22, 2022 | RCV000149882.10 | |
Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Dec 22, 2023 | RCV000201160.13 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Nov 1, 2022 | RCV000521440.21 | |
Likely pathogenic (1) |
no assertion criteria provided
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Dec 7, 2018 | RCV000984163.2 | |
Pathogenic (1) |
no assertion criteria provided
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Oct 22, 2020 | RCV001826801.2 | |
Pathogenic (1) |
criteria provided, single submitter
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Feb 27, 2023 | RCV003155089.2 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Mar 29, 2022 | RCV002483296.3 |
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. |
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Pathogenic
(Feb 07, 2017)
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criteria provided, single submitter
Method: clinical testing
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Duchenne muscular dystrophy
Affected status: yes
Allele origin:
germline
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Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital
Accession: SCV000692204.1
First in ClinVar: Feb 19, 2018 Last updated: Feb 19, 2018 |
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Pathogenic
(Feb 07, 2017)
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criteria provided, single submitter
Method: clinical testing
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Becker muscular dystrophy
Affected status: yes
Allele origin:
germline
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Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital
Accession: SCV000692205.1
First in ClinVar: Feb 19, 2018 Last updated: Feb 19, 2018 |
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Pathogenic
(Aug 04, 2014)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Athena Diagnostics
Accession: SCV000255707.3
First in ClinVar: Oct 19, 2015 Last updated: Oct 19, 2018 |
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Pathogenic
(Feb 01, 2022)
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criteria provided, single submitter
Method: clinical testing
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Becker muscular dystrophy
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004194010.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Dec 22, 2023)
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criteria provided, single submitter
Method: clinical testing
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Duchenne muscular dystrophy
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001205869.5
First in ClinVar: Apr 15, 2020 Last updated: Feb 14, 2024 |
Comment:
This sequence change affects a donor splice site in intron 15 of the DMD gene. RNA analysis indicates that disruption of this splice site induces … (more)
This sequence change affects a donor splice site in intron 15 of the DMD gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in a shortened protein product. This variant is present in population databases (rs373286166, gnomAD 0.005%). Disruption of this splice site has been observed in individuals with Becker or Duchenne muscular dystrophy (PMID: 17259292, 19937601, 27930565, 32194622). ClinVar contains an entry for this variant (Variation ID: 162497). Studies have shown that disruption of this splice site results in skipping of exon 15, but is expected to preserve the integrity of the reading-frame (PMID: 27930565). For these reasons, this variant has been classified as Pathogenic. (less)
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Likely pathogenic
(Apr 22, 2022)
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criteria provided, single submitter
Method: clinical testing
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Becker muscular dystrophy
Affected status: yes
Allele origin:
germline
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MGZ Medical Genetics Center
Accession: SCV002579670.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022
Comment:
ACMG criteria applied: PVS1, PM2_SUP
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Number of individuals with the variant: 1
Sex: female
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Pathogenic
(Jan 14, 2021)
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criteria provided, single submitter
Method: clinical testing
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Duchenne muscular dystrophy
(X-linked recessive inheritance)
Affected status: yes
Allele origin:
germline
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Genetics and Molecular Pathology, SA Pathology
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002761495.1
First in ClinVar: Dec 17, 2022 Last updated: Dec 17, 2022 |
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Pathogenic
(Mar 29, 2022)
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criteria provided, single submitter
Method: clinical testing
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Becker muscular dystrophy
Dilated cardiomyopathy 3B Duchenne muscular dystrophy
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002777815.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Pathogenic
(Jan 25, 2022)
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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: SCV000616994.5
First in ClinVar: Dec 19, 2017 Last updated: Mar 04, 2023 |
Comment:
Not observed at significant frequency in large population cohorts (gnomAD); Deletions involving coding exons in this gene are frequently reported as pathogenic, regardless of frame … (more)
Not observed at significant frequency in large population cohorts (gnomAD); Deletions involving coding exons in this gene are frequently reported as pathogenic, regardless of frame prediction (HGMD); Destroys the canonical splice donor site in intron 15, and cDNA analysis confirms that c.1812+1 G>A results in the in-frame skipping of exon 15 (Lerario et al., 2016); This variant is associated with the following publications: (PMID: 23871722, 25637381, 25525159, 27930565, 17259292, 32194622, 33726816, 33101180) (less)
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Pathogenic
(Feb 27, 2023)
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criteria provided, single submitter
Method: clinical testing
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Qualitative or quantitative defects of dystrophin
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV003844269.1
First in ClinVar: Mar 26, 2023 Last updated: Mar 26, 2023 |
Comment:
Variant summary: DMD c.1812+1G>A is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to … (more)
Variant summary: DMD c.1812+1G>A is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: One predict the variant abolishes the canonical 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 1.6e-05 in 182866 control chromosomes (gnomAD). c.1812+1G>A has been reported in the literature in individuals affected with Dystrophinopathies (example: Taylor_2007, Neri_2017, Wang_2019). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Ten clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Jun 30, 2021)
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criteria provided, single submitter
Method: clinical testing
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Duchenne muscular dystrophy
Becker muscular dystrophy Dilated cardiomyopathy 3B
Explanation for multiple conditions: Uncertain.
The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.
Affected status: yes
Allele origin:
germline
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North West Genomic Laboratory Hub, Manchester University NHS Foundation Trust
Accession: SCV004814236.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024 |
Comment:
Criteria Codes: PS3 PS4_Str PP4_Mod
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Pathogenic
(Nov 01, 2022)
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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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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001962614.15
First in ClinVar: Oct 08, 2021 Last updated: May 12, 2024 |
Number of individuals with the variant: 2
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Pathogenic
(Oct 22, 2020)
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no assertion criteria provided
Method: clinical testing
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Becker muscular dystrophy
Cardiomyopathy Duchenne muscular dystrophy Dystrophin deficiency
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV002092233.1
First in ClinVar: Feb 13, 2022 Last updated: Feb 13, 2022 |
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Likely pathogenic
(Jun 01, 2014)
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no assertion criteria provided
Method: research
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Muscular dystrophy, Becker
(X-linked inheritance)
Affected status: unknown
Allele origin:
germline
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CSER _CC_NCGL, University of Washington
Study: ESP 6500 variant annotation
Accession: SCV000190163.1 First in ClinVar: Jan 18, 2015 Last updated: Jan 18, 2015
Comment:
Variants classified for the Actionable exomic incidental findings in 6503 participants: challenges of variant classification manuscript
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Likely pathogenic
(Dec 07, 2018)
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no assertion criteria provided
Method: clinical testing
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Becker muscular dystrophy
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV001132169.1
First in ClinVar: Dec 23, 2019 Last updated: Dec 23, 2019 |
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Likely pathogenic
(Dec 07, 2018)
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no assertion criteria provided
Method: clinical testing
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Dilated cardiomyopathy 3B
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV001132170.1
First in ClinVar: Dec 23, 2019 Last updated: Dec 23, 2019 |
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Likely pathogenic
(Dec 07, 2018)
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no assertion criteria provided
Method: clinical testing
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Duchenne muscular dystrophy
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV001132171.1
First in ClinVar: Dec 23, 2019 Last updated: Dec 23, 2019 |
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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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The Genetic Landscape of Dystrophin Mutations in Italy: A Nationwide Study. | Neri M | Frontiers in genetics | 2020 | PMID: 32194622 |
Molecular Genetics Analysis of 70 Chinese Families With Muscular Dystrophy Using Multiplex Ligation-Dependent Probe Amplification and Next-Generation Sequencing. | Wang D | Frontiers in pharmacology | 2019 | PMID: 31404137 |
A case report with the peculiar concomitance of 2 different genetic syndromes. | Lerario A | Medicine | 2016 | PMID: 27930565 |
Actionable exomic incidental findings in 6503 participants: challenges of variant classification. | Amendola LM | Genome research | 2015 | PMID: 25637381 |
Rapid, comprehensive analysis of the dystrophin transcript by a custom micro-fluidic exome array. | Bovolenta M | Human mutation | 2012 | PMID: 22223181 |
Mutational spectrum of DMD mutations in dystrophinopathy patients: application of modern diagnostic techniques to a large cohort. | Flanigan KM | Human mutation | 2009 | PMID: 19937601 |
Array-MLPA: comprehensive detection of deletions and duplications and its application to DMD patients. | Zeng F | Human mutation | 2008 | PMID: 17854090 |
Measurement of the clinical utility of a combined mutation detection protocol in carriers of Duchenne and Becker muscular dystrophy. | Taylor PJ | Journal of medical genetics | 2007 | PMID: 17259292 |
Text-mined citations for rs373286166 ...
HelpRecord last updated May 12, 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.